Modern Use of Bryophytes as a Source of Secondary ... - MDPI

21
Citation: Dziwak, M.; Wróblewska, K.; Szumny, A.; Galek, R. Modern Use of Bryophytes as a Source of Secondary Metabolites. Agronomy 2022, 12, 1456. https://doi.org/ 10.3390/agronomy12061456 Academic Editor: Katja Witzel Received: 25 April 2022 Accepted: 13 June 2022 Published: 17 June 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). agronomy Review Modern Use of Bryophytes as a Source of Secondary Metabolites Michal Dziwak 1 , Katarzyna Wróblewska 1, * , Antoni Szumny 2 and Renata Galek 3 1 Department of Horticulture, Wroclaw University of Environmental and Life Sciences, Grunwaldzki 24a, 50-363 Wroclaw, Poland; [email protected] 2 Department of Food Chemistry and Biocatalysis, Wroclaw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroclaw, Poland; [email protected] 3 Department of Plant Genetics, Breeding and Seed Production, Wroclaw University of Environmental and Life Sciences, Grunwaldzki 24a, 50-363 Wroclaw, Poland; [email protected] * Correspondence: [email protected] Abstract: Bryophytes constitute a heterogeneous group of plants which includes three clades: ap- proximately 14,000 species of mosses (Bryophyta), 6000 species of liverworts (Marchantiophyta), and 300 species of hornworts (Anthocerotophyta). They are common in almost all ecosystems, where they play important roles. Bryophytes lack developed physical barriers, yet they are rarely attacked by herbivores or pathogens. Instead, they have acquired the ability to produce a wide range of secondary metabolites with diverse functions, such as phytotoxic, antibacterial, antifungal, insect antifeedant, and molluscicidal activities. Secondary metabolites in bryophytes can also be involved in stress tolerance, i.e., in UV-absorptive and drought- and freezing-tolerant activities. Due to these properties, for centuries bryophytes have been used to combat health problems in many cultures on different continents. Currently, scientists are discovering new, unique compounds in bryophytes with potential for practical use, which, in the age of drug resistance, may be of considerable importance. The aim of this review is to present bryophytes as a potential source of compounds with miscellaneous possible uses, with a focus on volatile compounds and antibacterial, antifungal, and cytotoxic potential, and as sources of materials for further promising research. The paper also briefly refers to the methods of compound extraction and acquisition. Formulas of compounds were drawn by the authors using ChemDraw software (PerkinElmer, Boston, MA, USA) with reference to data published in various papers, the ACD/Labs dictionary database, PubChem, and Scopus. The data were gathered in February 2022. Keywords: Bryophyta; volatile compounds; antimicrobial activity; antibacterial and antifungal potential; cytotoxic compounds 1. Introduction Bryophytes constitute a heterogeneous group of plants which includes three clades: mosses (Bryophyta), liverworts (Marchantiophyta), and hornworts (Anthocerotophyta) [1,2]. Their characteristic feature is the alternation of generations with the dominance of the haploid gametophyte. There are about 14,000 species of mosses, 6000 species of liverworts, and 300 species of hornworts in the world [3]. Representatives of this group are common in all ecosystems (except salt water ecosystems), where they play important roles [4]. Bryophytes can be found in tropical forests [5,6], Antarctica [7,8], and deserts [9–11], as well as other sites difficult for plants to access. Due to their tolerance of lack of light, they can develop in places with limited access to light, e.g., caves [12–14]. Bryophytes lack developed physical barriers, but they are rarely attacked by herbivores and pathogens [15]. This is due to their ability to produce a wide range of secondary metabolites which allow them to survive unfavorable abiotic conditions, protecting them against potential biotic stresses (Table 1). Agronomy 2022, 12, 1456. https://doi.org/10.3390/agronomy12061456 https://www.mdpi.com/journal/agronomy

Transcript of Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Page 1: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Citation Dziwak M Wroacuteblewska

K Szumny A Galek R Modern

Use of Bryophytes as a Source of

Secondary Metabolites Agronomy

2022 12 1456 httpsdoiorg

103390agronomy12061456

Academic Editor Katja Witzel

Received 25 April 2022

Accepted 13 June 2022

Published 17 June 2022

Publisherrsquos Note MDPI stays neutral

with regard to jurisdictional claims in

published maps and institutional affil-

iations

Copyright copy 2022 by the authors

Licensee MDPI Basel Switzerland

This article is an open access article

distributed under the terms and

conditions of the Creative Commons

Attribution (CC BY) license (https

creativecommonsorglicensesby

40)

agronomy

Review

Modern Use of Bryophytes as a Source ofSecondary MetabolitesMichał Dziwak 1 Katarzyna Wroacuteblewska 1 Antoni Szumny 2 and Renata Galek 3

1 Department of Horticulture Wroclaw University of Environmental and Life Sciences Grunwaldzki 24a50-363 Wrocław Poland 107077studentupwredupl

2 Department of Food Chemistry and Biocatalysis Wroclaw University of Environmental and Life SciencesNorwida 25 50-375 Wrocław Poland antoniszumnyupwredupl

3 Department of Plant Genetics Breeding and Seed Production Wroclaw University of Environmental and LifeSciences Grunwaldzki 24a 50-363 Wrocław Poland renatagalekupwredupl

Correspondence katarzynawroblewskaupwredupl

Abstract Bryophytes constitute a heterogeneous group of plants which includes three clades ap-proximately 14000 species of mosses (Bryophyta) 6000 species of liverworts (Marchantiophyta) and300 species of hornworts (Anthocerotophyta) They are common in almost all ecosystems where theyplay important roles Bryophytes lack developed physical barriers yet they are rarely attacked byherbivores or pathogens Instead they have acquired the ability to produce a wide range of secondarymetabolites with diverse functions such as phytotoxic antibacterial antifungal insect antifeedantand molluscicidal activities Secondary metabolites in bryophytes can also be involved in stresstolerance ie in UV-absorptive and drought- and freezing-tolerant activities Due to these propertiesfor centuries bryophytes have been used to combat health problems in many cultures on differentcontinents Currently scientists are discovering new unique compounds in bryophytes with potentialfor practical use which in the age of drug resistance may be of considerable importance The aim ofthis review is to present bryophytes as a potential source of compounds with miscellaneous possibleuses with a focus on volatile compounds and antibacterial antifungal and cytotoxic potential andas sources of materials for further promising research The paper also briefly refers to the methods ofcompound extraction and acquisition Formulas of compounds were drawn by the authors usingChemDraw software (PerkinElmer Boston MA USA) with reference to data published in variouspapers the ACDLabs dictionary database PubChem and Scopus The data were gathered inFebruary 2022

Keywords Bryophyta volatile compounds antimicrobial activity antibacterial and antifungalpotential cytotoxic compounds

1 Introduction

Bryophytes constitute a heterogeneous group of plants which includes three cladesmosses (Bryophyta) liverworts (Marchantiophyta) and hornworts (Anthocerotophyta) [12]Their characteristic feature is the alternation of generations with the dominance of the haploidgametophyte There are about 14000 species of mosses 6000 species of liverworts and300 species of hornworts in the world [3] Representatives of this group are common in allecosystems (except salt water ecosystems) where they play important roles [4] Bryophytescan be found in tropical forests [56] Antarctica [78] and deserts [9ndash11] as well as other sitesdifficult for plants to access Due to their tolerance of lack of light they can develop in placeswith limited access to light eg caves [12ndash14] Bryophytes lack developed physical barriersbut they are rarely attacked by herbivores and pathogens [15] This is due to their ability toproduce a wide range of secondary metabolites which allow them to survive unfavorableabiotic conditions protecting them against potential biotic stresses (Table 1)

Agronomy 2022 12 1456 httpsdoiorg103390agronomy12061456 httpswwwmdpicomjournalagronomy

Agronomy 2022 12 1456 2 of 21

For centuries bryophytes have been used to combat health problems in many cultureson different continents According to Indian and Chinese medicine the spectrum oftheir applications is very wide from being used to fight fevers through to treating skininfections and relieving pain [1617] Native Americans used a mixture of moss ash andhoney as a disinfectant for wounds [17] During World War I dried sphagnum mosswas used in Canada as a replacement for bandages Its effectiveness is related to its highabsorbency and bactericidal properties [18] After thorough examinations some of thespecies that were formerly considered to be therapeutic were found to be ineffective oreven in some cases toxic yet the aseptic and anti-cancer properties of numerous specieshave been confirmed They have therefore been the object of increasing scientific interestA significant number of bryophyte secondary metabolites have potential pharmacologicaleconomic or biotechnological uses The biologically active compounds that can be obtainedfrom bryophytes include antioxidants compounds toxic to specific groups of organisms(potential plant-protection agents) inhibitors of certain enzymes anti-cancer and anti-HIV-1 compounds neurotrophic compounds and compounds that relax muscles andstrengthen the heart They are also associated with numerous aromas (of carrots cedartrees mushrooms) pungency and bitterness [19] The aim of this review is to presentbryophytes as a potential source of compounds with miscellaneous possible uses and assources of materials for further promising research The paper also briefly refers to themethods of compound extraction and acquisition

Table 1 The main classes of secondary metabolites among bryophytes and their potential activities

Class

Potential Activity

Ant

ibac

teri

alan

dFu

ngic

idal

Cyt

otox

ic

Inse

ctic

idal

and

Mol

lusc

icid

al

Phyt

otox

ic

Col

d-To

lera

nt

Dro

ught

-Tol

eran

t

Ant

i-U

V

Ref

eren

ces

Benzenoids + + + [320ndash22]

Bibenzyls andbis(bibenzyls) + + + + + [319ndash24]

Fatty acidderivatives + + [320ndash25]

Flavonoids + + + [320ndash2225]

Phenylpropanoids + + + [32022ndash25]

Terpenes andterpenoids + + + + [319ndash27]

2 Ethnopharmacology

In ancient times medical utility was indicated by the appearance of a plant ie theshape and structure of its organs It was a view presented by Paracelsus as the lsquodoctrineof signaturesrsquo Following this belief the species Polytrichum commune Hedw has beenused to improve the condition of the hair Tribal cultures of South India used hair-likethallus of Frullania ericoides (Nees) Mont in a similar way The Irular tribe of the Attappadyvalleys used the thalloid gametophytes of Targionia hypophylla L to treat skin conditionsdue to its characteristic rough surface [17] The thallus of Plagiochasma appendiculatum Lehmamp Lindenb was used for skin diseases by Gaddi tribes of Himachal Pradesh India [14]American tribes used some mosses as remedies for burns the Gasuite Indians used speciesfrom the genera Philonotis (Hedw) Brid Bryum Hedw Mnium Hedw and also from theHypnaceae family while Polytrichum juniperinum Hedw was used by indigenous Alaskanand Cheyenne populations [23] Alaskan Natives also made ointment from Sphagnumleaves mixed with tallow and grease to treat cuts [28]

Agronomy 2022 12 1456 3 of 21

Pre-Columbian Mesoamerican cultures found uses for 36 species of bryophytes forceremonial craft and medical purposes [29] Some of them were mentioned in Libellus deMedicinalibus Indorum Herbis (1552)mdashthe oldest report of the medical use of bryophytesin Mesoamerica [30] Marchantia sp L was used in combination with Begonia sp L andLithanchne pauciflora (Sw) PBeauv to treat mouth sores and fever [31] Headaches weretreated by washes made of Braunia secunda (Hook) Bruch amp Schimp boiled in water [29]Tea prepared from Pleurochaete squarrosa (Brid) Lindb was used to relieve stomach acheand as a compress favoring the healing of wounds [29] The moss Sematophyllum adnatum(Michx) E Britton was used to prepare medicinal tea [18] Dendropogonella rufescens(Schimp) E Britton was used by the Zapotec community to treat the discomfort of womenafter childbirth Smoking this moss with stalk of Agave americana L and corn ear stylesgave relief for muscle and bone pain [32] Currently D rufescens is prepared as a drinkto increase the appetite for kidney and lung health and as a treatment for blindness anddiabetes-related ailments [32]

The bryophytes also have many other medical uses The liverwort Conocephalumconicum (L) Dum was used in the form of a decoction as an antibacterial antifungaland antipyretic agent It was applied to treat wounds swelling burns and snake bitesMarchantia polymorpha L was used as a medicine for inflammation liver problems bitesand cuts and as a diuretic [1633] while Frullania tamarisci (L) Dumort was utilized asan antiseptic remedy [16] Riccia L species was used to cure ringworm the fungal skininfection [28] Reboulia hemisphaerica L Raddi was used for hemostasis and to treat blotchesexternal wounds and bruises Funaria hygrometrica Hedw served as a hemostatic to curepulmonary tuberculosis hematemesis bruises and athletersquos foot dermatophytosis [33]The moss Bryum argenteum Hedw was valued as an antipyretic and antifungal medicineDue to their antimicrobial properties members of the Sphagnaceae family were used tocover wounds skin ailments and to treat eye diseases [16] During the RussondashJapaneseWar Sphagnum L mosses were used by the Japanese as a first-aid dressing on a largescale [28] Furthermore during World War I dried Sphagnum sp was used in BritainCanada and Germany as a cheap substitute for cotton bandages [1834] The aquatic mossFontinalis antipyretica Hedw boiled with beer was used as a footbath to treat chest feverfever microbial infections and for detoxication [33]

3 Secondary Metabolites

The species of bryophytes express diverse functions such as phytotoxic antibacterialantifungal insect antifeedant and molluscicidal activities [19] They can be involvedin stress tolerance ie in UV-absorptive and drought- and freezing-tolerant activities(Table 1) [319ndash26] Both extracts and isolated compounds of bryophytes are very popular instudies as sources for new applications Treatment with extracts allows examination of theactivities of all compounds contained in the plant material including their interactions [35]An important element in the preparation of extracts is the selection of appropriate solventsas this determines the extracted compounds With proper extraction methods extractsoften prove to be as effective as commercially synthesized substances

Among the known species of bryophytes biologically active compounds from differ-ent classes can be mentioned such as benzenoids bibenzyls bis(bibenzyl)s flavonoidsterpenoids phenylpropanoids and derivatives of fatty acids The spectrum of applicationof compounds contained in this group of plants is considerable as every group has atleast a few activities (Table 1) Unfortunately their use is hampered by the fact that somesubstances have not yet been identified and tested

31 Volatile Compounds

Due to the presence of oil bodies liverworts are characterized by the widest range ofaromas among bryophytes [36] The sources of odors are volatile mono- and sesquiterpenesand terpenoids as well as low-molecular weight derivatives of fatty acids or phenyl-propanoids [19] Miscellaneous pleasant fragrances with potential for use in perfumery

Agronomy 2022 12 1456 4 of 21

pharmacy and the food industry can be found in liverworts but there are also odors thatcause unpleasant sensations Some of the aromas are specific only to a single species ofliverwort Valarenzo et al [37] screened volatile metabolites in four liverwort speciesDepending on the species studied it was not possible to identify 10 to 15 of the essentialoil compounds and they require further research The unknown compounds may includemetabolites unique to bryophytes to specific families or to single species Essential oilshave also been found in mosses [38] There have been several reports that some of themshow antimicrobial activity against bacteria and fungi [39ndash41]

Unique aromas can also be found among other bryophytes eg Takakia lepidozioides SHatt amp Inoue is characterized by an aromatic blend of cinnamon and roasted wheat dueto the presence of coumarin [42] (Table 2) The smells of bryophytes depend not only oncontents of volatile secondary metabolites in their essential oils (Table 2) but also on planthabitat conditions eg Frullania species produce tamariscol (1 Figure 1) only when grownin high mountain sites [19] According to Sakurai et al [43] the aroma of the liverwortCyathodium foetidissimum Schiffn collected in Tahiti in 2016 was pleasant described aslsquonostalgicrsquo or a lsquochest of drawersrsquo in contrast to the same species found on Ua Huka inMarquesas Islands in 2009 [44] which exuded the smell of urine and feces These islandsare located in French Polynesia about 1400 km away

Table 2 Selected species of bryophytes their aromas and main volatile compounds

Species Family Major VolatileComponents 1 Odor Ref

Asterella speciesPBeauv Aytoniaceae Skatole (2) Feces-like unpleasant [45]

Conocephalum conicum(L) Dum Conocephalaceae

(ndash)-sabinene (+)-bornylacetate

methyl cinnamate (3)

Camphoraceousdistinctly mushroomy [4647]

Cyathodium foetidissimumSchiffn Cyathodiaceae

Skatole (2)bicyclogermacrene

and isolepidozene (5)lunularin (6)

Feces urine unpleasant [434849]

Frullania tamarisci(L) DumortF nepalensis

(Spreng) Lehm amp LindenbF asagrayana

Montagne

Frullaniaceae Tamariscol (1) Oak moss-like [5051]

Jungermannia obovataNees Jungermanniaceae 4-hydroxy-4-

methylcyclohex-2-en-1-one Carrot-like [1952]

Leptolejeunea ellipticaLehm amp Lindenb Lejeuneaceae p-ethylphenol (7)

p-ethyl phenyl acetate Naphtalene and dried fish [5354]

Lophocolea heterophylla(Schrad) DumortLophocolea bidentata

(L) Dumort

Lophocoleaceae (ndash)-2-methylisoborneolgeosmin (8) Strong and distinctly mossy [1955]

Mannia fragrans(Balbis) Frye et LClark Aytoniaceae Grimaldone (9) Strong sweet-mossy [5657]

Plagiochila sciophilaNees Plagiochilaceae Bicyclohumulenone (10) Sweet-mossy and woody [19]

Plagiochila rutilansLindenb Plagiochilaceae

R-pulegone (11) and severalother menthanemonoterpenoids

Peppermint-like [5859]

Symphyogyna brongniartiiMont Pallaviciniaceae Geosmin (8) Distinctly earthymusty [60]

Takakia lepidozioidesS Hatt amp Inoue Takakiaceae Coumarin (12) Cinnamon and burnt

wheat [44]

1 Bold numbers refer to the chemical structures of compounds are presented in Figure 1

Agronomy 2022 12 1456 5 of 21

Agronomy 2022 12 x FOR PEER REVIEW 5 of 21

Plagiochila rutilans Lindenb

Plagiochilaceae R-pulegone (11) and several other

menthane monoterpenoids Peppermint-like [5859]

Symphyogyna brongniartii Mont

Pallaviciniaceae Geosmin (8) Distinctly earthymusty

[60]

Takakia lepidozioides S Hatt amp Inoue

Takakiaceae Coumarin (12) Cinnamon and burnt wheat

[44]

1 Bold numbers refer to the chemical structures of compounds are presented in Figure 1

Figure 1 Chemical structures of compounds mentioned in Table 2 (1 tamariscol 2 scatole 3 methyl cinnamate 4 bicyclogermacrene 5 isolepidozene 6 lunularin 7 p-ethylphenol 8 geosmin 9 gri-maldone 10 bicyclohumulenone 11 R-pulegone 12 coumarin)

Figure 1 Chemical structures of compounds mentioned in Table 2 (1 tamariscol 2 scatole3 methyl cinnamate 4 bicyclogermacrene 5 isolepidozene 6 lunularin 7 p-ethylphenol8 geosmin 9 grimaldone 10 bicyclohumulenone 11 R-pulegone 12 coumarin)

32 Antimicrobial Compounds and Extracts

Secondary metabolites found in bryophytes such as flavonoids terpenes fatty acidderivatives bibenzyls and bis(bibenzyl)s constitute a chemical lsquobarrierrsquo against potentialpathogens justifying the use of bryophyte extracts in the folk medicine of many culturesin particular the use of bryophytes in the treatment of infections and wound cleansingResearch on bryophytes has confirmed their antimicrobial properties Table 3 presentsexamples of extracts obtained from bryophytes and the antibacterial and antifungal ac-

Agronomy 2022 12 1456 6 of 21

tivities of their extracts against selected pathogens Gram-negative bacteria show greatersensitivity to extracts obtained from bryophytes This makes them potential complementsfor antibiotics as conventional antibiotics tend to be more active against Gram-positivebacteria [1861] This phenomenon is rare in higher plants [62] The metabolites showingantibacterial activity isolated from the extracts are unique to bryophytes Among themlunularin (21) marchantin A (29) polygodial (30) riccardiphenol C (32) and sacculatal wereisolated (Table 4 Figure 2) They show activity against ie Acinetobacter calcoaceticusBacillus cereus B subtilis Cryptococcus neoformans Pseudomonas aeruginosa Salmonellatyphimurium Staphylococcus aureus and Streptococcus mutans

Table 3 Antimicrobial activities of some bryophyte extracts

Division Species Extracts Tested Bacteria Tested Fungi Ref

Bryo

phyt

a

Atrichumundulatum

(Hedw) PBeauv

Waterethanol

Bacillus mycoidesEscherichia coli

Proteus mirabilisStaphylococcus aureus

Salmonella typhii

Aspergillus fumigatusFusarium oxysporum [6364]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Bryumargenteum

HedwEthanol

Escherichia coliBacillus subtilis

Micrococcus luteusStaphilococcus aureus

Aspergillus nigerPenicillium ochrochloron

Candida albicansTrichophyton mentagrophyes

[67]

Dicranum scopariumHedw Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureusStreptococcus pyogenes

NT [68]

Fontinalis antipyreticaHedw Methanol

Escherichia coliSalmonella enteritidisShigella epidermidis

Bacillus subtilisMicrococcus flavus

Aspergillus flavusA fumigatus

A nigerPenicillium funiculosum

P ochrochloronTrichoderma viride

[69]

Hypnum cupressiformeHedw

Methanol

Bacillus subtilisEscherichia coli

Micrococcus flavusShigella enteritidis

S epidermidis

Aspergillus flavusA fumigatus

A nigerPenicillium funiculosum

P ochrochloronTrichoderma viride

[69]

Water NS Candida albicansSaccharomyces cerevisiae [70]

Plagiomniumcuspidatum

(Hedw) TJKopn-hexane

Bacillus subtilisMoraxella catarrhalis

Staphylococcus aureusShigella epidermidis

Streptococcus pyogenesS pneumonianiae

NT [71]

Agronomy 2022 12 1456 7 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Polytrichum communeHedw

Water

Escherichia coliEnterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NT [72]

Chloroformethanol

Bacillus cereusEscherichia coli

Enterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NS [73]

Polytrichumjuniperinum

Hedw

MethanolBacillus subtilis

Pseudomonas aeruginosaStaphylococcus aureus

NT [74]

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Syntrichiaruralis

(Hedw) F Weber amp DMohr

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Mar

chan

tioph

yta

Bazzania trilobata L

Dichloromethanemethanol NT

Botrytis cinereaCandida albicans

Cladosporium cucumerinumPhythophthora infestans

Pyricularia oryzaeSeptoria tritici

[75]

EthanolBacillus subtilis

Listeria monocytogenesStaphylococcus aureus

NS [76]

Frullaniadilatata

(L) Dumort

Waterethanol Staphylococcus aureus NT [77]

Lophozia ventricosa(Dicks) Dumort

Methanolethyl acetate

Bacillus cereusListeria monocytogenes

Micrococcus flavusStaphylococcus aureus

Aspergillus nigerA fumigatesA ochraceusA versicolor

Penicillium funiculosumP ochrochloron

Trichoderma viride

[78]

Agronomy 2022 12 1456 8 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Lunulariacruciata

(L) Lindb

Acetonechloroform

ethanolmethanol

water

Agrobacterium tumefaciensStaphylococcus aureusShigella epidermidis

Streptococcus faecalisProteus mirabilis

P vulgarisPseudomonas aeruginosa

Escherichia coliSalmonella typhi

Klebsiella pneumoniaeEnterobacter cloacae

E aerogenesCitrobacter diversus

Bacillus subtilisXanthomonas phoseoliErwinia chrysanthemi

NS [7980]

Marchantia polymorphaL

Chloroformmethanol

Escherichia coliStaphylococcus aureus

Proteus mirabilisPasturella multocidaXanthomonas oryzae

Candida albicansFusarium oxysporum

Rhizoctonia solaniSclerotium rolfsii

Trichophyton mentagrohtytesTilletia indica

[8182]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Porellaarboris-vitae

(With) Grolle

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

Pichia anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[83]

RebouliaHemisphaerica(L)

RaddiMethanol

Bacillus cereus B subtilisEscherichia coli

Enterococcus faecalisPseudomonas aeruginosa

Staphylococcus aureus

Aspergillus nigerPenicillium notatum [84]

Scapania asperaM Bernet amp Bernet

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

P anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[61]

Targioniahypophylla L Methanol

Bacillus substilisEscherichia coli

Staphylococcus aureus

Aspergillus nigerBotrytis cinerea

Penicillium chrysogenumP expansum

Trichoderma viridae

[8586]

Distillation NTmdashnot tested NSmdashnot shown

Agronomy 2022 12 1456 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)Nees Dumortieraceae Pseudomonas aeruginosa (MIC

64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC125 microgmL)

Bacillus cereus (125 microgmL)Bacillus megaterium (MIC

25 microgmL)Bacillus subtilis (MIC25 microgmL)

Cryptococcus neoformans (MIC125 microgmL) Staphylococcus aureus

(MIC 313ndash25)Salmonella typhimurium (MIC

100 microgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50100 microgmL) [19]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae Streptococcus mutans (LD50

8 microgmL) [19]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdashminimuminhibitory concentration Bold numbers refer to the chemical structures o Bold numbers refer to the chemicalstructures of compounds are presented in Figures 1 and 2

Agronomy 2022 12 x FOR PEER REVIEW 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)

Nees Dumortieraceae Pseudomonas aeruginosa (MIC 64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC 125 μgmL)

Bacillus cereus (125 μgmL)

Bacillus megaterium (MIC 25 μgmL)

Bacillus subtilis (MIC25 μgmL)

Cryptococcus neoformans (MIC 125 μgmL)

Staphylococcus aureus (MIC 313ndash25)

Salmonella typhimurium (MIC 100 μgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50 100 μgmL) [19]

Sacculatal (15) Pellia endiviifolia (Dicks)

Dumort Pelliaceae Streptococcus mutans (LD50 8 μgmL) [19]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdash

minimum inhibitory concentration Bold numbers refer to the chemical structures o Bold numbers

refer to the chemical structures of compounds are presented in Figures 1 and 2

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygo-

dial 15 sacculatal 16 riccardiphenol C)

Apart from their antibacterial potential bryophyte extracts show antifungal proper-

ties The results of the research show that the extracts of certain species of mosses and

liverworts do not exhibit these properties despite their antibacterial effects [737980]

Such selectivity may have industrial or medical applications [4791ndash93] On the other

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygodial15 sacculatal 16 riccardiphenol C)

Agronomy 2022 12 1456 10 of 21

Apart from their antibacterial potential bryophyte extracts show antifungal proper-ties The results of the research show that the extracts of certain species of mosses andliverworts do not exhibit these properties despite their antibacterial effects [737980] Suchselectivity may have industrial or medical applications [4791ndash93] On the other hand theisolated antifungal substances show activity against numerous pathogenic fungi (Table 5Figure 3) [7588ndash9094ndash97]

Table 5 Antifungal activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Asterelin A (17 R=H)Asterelin B (18 R=Me)

Asterella angusta(Stephani) Pandeacute KPSrivast amp Sultan Khan

Aytoniaceae Candida albicans [94]

Bazzanin B (19 R=Cl)Bazzanin S (20 R=H) Bazzania trilobata L Lepidoziaceae

Botrytis cinerea (IC50 189)Cladosporium cucumerinum (IC50

175)Pyricularia oryzae (IC50 39)

Zymoseptoria tritici (IC50 235)

[75]

Isoplagiochin D (21)Bazzania trilobata LLepidozia incurvata

LindenbLepidoziaceae Zymoseptoria tritici (IC50 159) [95]

Isoriccardin C (22)Plagiochasmaintermedium

Lindenb amp GottscheAytoniaceae Candida albicans [95]

Gymnomitrol (23)Bazzania trilobata L

Gymnomitrion obtusum(Lindb) Pears

LepidoziaceaeGymnomitriaceae

Phytophthora infestansPyricularia oryzae

Zymoseptoria tritici[7598]

Marchantin A (13) Marchantia species L Marchantiaceae

Aspergillus niger (MIC25-100 microgmL)

Pyricularia oryzae (MIC125 microgmL)

Rhizoctonia solani (MIC 50 microgmL)Saccharomyces cerevisiae (MIC

313 microgmL)Trichophyton mentagrophytes (MIC

313 microgmL)

[8889]

Marchantin H (24)

Marchantia polymorphaL

Plagiochasmaintermedium Lindenb amp

Gotische

MarchantiaceaAytoniaceae Candida albicans (MIC 256 microgmL) [97]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorphaL Marchantiaceae Candida albicans [96]

Riccardin C (27)

Asterella angusta(Stephani) Pandeacute KP

Sri-vast amp Sultan KhanPlagiochasma

intermedium Lindenb ampGotische

AytoniaceaeAytoniaceae Candida albicans [97]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Candida albicans

Trichophyton mtagropbytes [90]

IC50 the concentration of a drug that is required for 50 inhibition in vitro MICmdashminimum inhibitory concentra-tion Bold numbers refer to the chemical structures o Bold numbers refer to the chemical structures of compoundsare presented in Figures 2 and 3

Agronomy 2022 12 1456 11 of 21Agronomy 2022 12 x FOR PEER REVIEW 11 of 21

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 asterelin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardin C 23 gym-nomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH 27 riccardin C)

33 Cytotoxic Compounds The bryophyte extracts apart from their antimicrobial activities showed cytotoxic

activities in vitro [387] The same was corroborated for some particular compounds Some of them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 aster-elin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardinC 23 gymnomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH27 riccardin C)

33 Cytotoxic Compounds

The bryophyte extracts apart from their antimicrobial activities showed cytotoxicactivities in vitro [387] The same was corroborated for some particular compounds Someof them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Agronomy 2022 12 1456 12 of 21

PC3 These compounds were tested on several human and mouse tumor lines breast cancerMCF-7 cellosaurus P388 chemoresistant prostate cancer PC3 glioblastoma multiforme U-251 leukemia HL-60 liver cancer HepG2 melanoma RPMI-7951 and monocytic leukemiaU937 (Table 6 Figure 4)

Table 6 Cytotoxic compounds isolated from bryophytes with modern uses

Compounds Species Family Activity Against Ref

Jungermannenone A(28 R=OH)

Jungermannenone B(29 R=H)

Jungermannia species L Jungermanniaceae

Human leukemia HL-60 cells(JA IC50

1 13 microM)PC3 (JA 15 micromolL JB

5 micromolL)

[399]

Lunularin (6) Dumortiera hirsuta (Sw)Nees Weisnerellaceae HepG2 (IC50 = 74 microgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Human MCF-7 breastcancer (IC50 40 microgmL)

chemoresistant prostate cancerPC3 cells

A375 melanoma cells(IC50 = 745ndash1197 microgmL)

[3100101]

Marsupellone (30) Marsupella emarginata(Ehrh) Dumort Gymnomitriaceaea P388 cancer cell line

(ID50 1 microgmL) [88]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorpha LSchistochila glaucescens

(Hook) AEvans

MarchantiaceaeSchistochilaceae P388 cell line (IC50 8ndash18 microgmL) [102]

Pallidisetin A (31)Pallidisetin B (32)

Polytrichum pallidisetumFunck Polytrichaceae

Melanoma (RPMI-7951)Glioblastoma multiforme

(U-251)[103]

Plagiochin E (33) Plagiochasm intermediumLindenb amp Gottsche Aytoniaceae Chemoresistant prostate cancer

PC3 cells (IC50 599 micromolL) [100]

Riccardin C (27)

Plagiochasma intermediumLindenb amp Gottsche

Reboulia hemisphaerica (L)Raddi

Aytoniaceae Chemoresistant prostate cancerPC3 cells (IC50 322 micromolL) [100104]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae BSC cells [90]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae

Human melanoma(IC50 2ndash4 micromolL) Lu1

(IC50 57 micromolL)KB (IC50 32 micromolL)

LNCaP and ZR-75-1 cells(IC50 76 micromolL)

[105]

Trewiasine (34)

Isothecium subdiversiformeBroth

Thamnobryum sandeiBesch

BrachytheciaceaeNeckeraceae

U937 cells ascitic tumors S180hepatoma U14 solid tumor

Lewis lung carcinoma[106]

1 IC50 the concentration of a drug that is required for 50 inhibition of cell growth in vitro Bold numbersrefer to the chemical structures o Bold numbers refer to the chemical structures of compounds are presented inFigures 3 and 4

Agronomy 2022 12 1456 13 of 21Agronomy 2022 12 x FOR PEER REVIEW 13 of 21

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenone B R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds In several species of the Radula Dumort genus cannabinoid compounds have been

discovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated from Radula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor) Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests on mouse brains showed that this compound is bioavailable and selectively binds to CB1 and CB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to Δ9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenoneB R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds

In several species of the Radula Dumort genus cannabinoid compounds have beendiscovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated fromRadula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor)Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests onmouse brains showed that this compound is bioavailable and selectively binds to CB1 andCB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to ∆9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

References1 Cole TCH Hilger HH Goffinet B Bryophyte Phylogeny Poster (BPP) PeerJ Prepr 2019 7 e27571v3 [CrossRef]2 de Sousa F Foster PG Donoghue PCJ Schneider H Cox CJ Nuclear Protein Phylogenies Support the Monophyly of the

Three Bryophyte Groups (Bryophyta Schimp) New Phytol 2019 222 565ndash575 [CrossRef]

Agronomy 2022 12 1456 16 of 21

3 Asakawa Y Ludwiczuk A Nagashima F Chemical Constituents of Bryophytes Bio-and Chemical Diversity Biological Activityand Chemosystematics In Progress in the Chemistry of Organic Natural Products Springer Vienna Austria 2013 Volume 95pp 1ndash796 ISBN 9783709110843

4 Tuba Z Slack NG Stark LR (Eds) Bryophyte Ecology and Climate Change Cambridge University Press Cambridge UK 2011ISBN 978-0-521-75777-5

5 Frahm JP Manual of Topical Bryology Trop Bryol 2003 23 196 [CrossRef]6 Costa DP Nadal F da Rocha TC The First Botanical Explorations of Bryophyte Diversity in the Brazilian Amazon Mountains

High Species Diversity Low Endemism and Low Similarity Biodivers Conserv 2020 29 2663ndash2688 [CrossRef]7 Cannone N Convey P Guglielmin M Diversity Trends of Bryophytes in Continental Antarctica Polar Biol 2013 36 259ndash271

[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

Change In Photosynthesis in Bryophytes and Early Land Plants Hanson DT Rice SK Eds Springer Dordrecht The Netherlands2014 pp 309ndash324 ISBN 978-94-007-6988-5

9 Smith RJ Stark LR Habitat vs Dispersal Constraints on Bryophyte Diversity in the Mojave Desert USA J Arid Environ 2014102 76ndash81 [CrossRef]

10 Stark LR Bisexuality as an Adaptation in Desert Mosses Am Midl Nat 1983 110 445ndash448 [CrossRef]11 Scott GAM Desert Bryophytes In Bryophyte Ecology Smith AJE Ed Springer Dordrecht The Netherlands 1982 pp 105ndash122

ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

39 587ndash596 [CrossRef]14 Ren H Wang F Ye W Zhang Q Han T Huang Y Chu G Hui D Guo Q Bryophyte Diversity Is Related to Vascular

Plant Diversity and Microhabitat under Disturbance in Karst Caves Ecol Indic 2021 120 106947 [CrossRef]15 Von Reuszlig SH Koumlnig WA Olefinic Isothiocyanates and Iminodithiocarbonates from the Liverwort Corsinia coriandrina Eur J

Org Chem 2005 2005 1184ndash1188 [CrossRef]16 Chandra S Chandra D Barh A Pankaj Pandey RK Sharma IP Bryophytes Hoard of Remedies an Ethno-Medicinal

Review J Tradit Complement Med 2016 7 94ndash98 [CrossRef] [PubMed]17 Krishnan VGM Pradeep DP Aswathy JM Krishnan R Lubaina AS Murugan K Wonder Herbals-Bryophytes of

the Ponmudi Hills of Southern Western Ghats Window Into the Need for Conservation World J Pharm Pharm Sci 2014 31548ndash1562

18 Glime J Medical Uses Medical Conditions In Bryophyte Ecology Michigan Technological University Houghton MI USA 2017p 5 Available online httpsdigitalcommonsmtueduoabooks4 (accessed on 6 October 2021)

19 Asakawa Y Biologically Active Compounds from Bryophytes Pure Appl Chem 2007 79 557ndash580 [CrossRef]20 Xie CF Lou HX Secondary Metabolites in Bryophytes An Ecological Aspect Chem Biodivers 2009 6 303ndash312 [CrossRef]21 Asakawa Y Ludwiczuk A Novakovic M Bukvicki D Anchang KY Bis-Bibenzyls Bibenzyls and Terpenoids in 33 Genera

of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

Austria 1982 pp 1ndash28523 Sabovljevic MS Sabovljevic AD Ikram NKK Peramuna A Bae H Simonsen HT BryophytesmdashAn Emerging Source for

Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

110649 [CrossRef]27 Zhu MZ Li Y Zhou JC Lu JH Zhu RX Qiao YN Zhang JZ Zong Y Wang X Jin XY et al Terpenoids from

the Chinese Liverwort Odontoschisma Grosseverrucosum and Their Antifungal Virulence Activity Phytochemistry 2020 174[CrossRef]

28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

41ndash49 [CrossRef]

Agronomy 2022 12 1456 17 of 21

35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

37 Valarezo E Tandazo O Galaacuten K Rosales J Beniacutetez Aacute Volatile Metabolites in Liverworts of Ecuador Metabolites 2020 10 92[CrossRef]

38 Saritas Y Sonwa MM Iznaguen H Koumlnig WA Muhle H Mues R Volatile Constituents in Mosses (Musci) Phytochemistry2001 57 443ndash457 [CrossRef]

39 Tosun G Yaylı B Oumlzdemir T Batan N Bozdeveci A Yaylı N Volatiles and Antimicrobial Activity of the Essential Oils ofthe Mosses Pseudoscleropodium purum Eurhynchium striatum and Eurhynchium angustirete Grown in Turkey Rec Nat Prod 2015 9237ndash242

40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

43 Sakurai K Tomiyama K Kawakami Y Yaguchi Y Asakawa Y Characteristic Scent from the Tahitian Liverwort CyathodiumFoetidissimum J Oleo Sci 2018 67 1265ndash1269 [CrossRef]

44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

45 Asakawa Y Joulain D Chemical Constituents of Unidentified Malaysian Liverwort Astrella () Species J Hattori Bot Lab 1995188 183ndash188 [CrossRef]

46 Toyota M Saito T Matsunami J Asakawa Y A Comparative Study on Three Chemo-Types of the Liverwort ConocephalumConicum Using Volatile Constituents Phytochemistry 1997 44 1265ndash1270 [CrossRef]

47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

48 Ludwiczuk A Komala I Pham A Bianchini JP Raharivelomanana P Asakawa Y Volatile Components from SelectedTahitian Liverworts Nat Prod Commun 2009 4 1387ndash1392 [CrossRef]

49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

51 Pannequin A Tintaru A Desjobert JM Costa J Muselli A New Advances in the Volatile Metabolites of Frullania tamarisciFlavour Fragr J 2017 32 409ndash418 [CrossRef]

52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

64 Vats S Alam A Antibacterial Activity of Atrichum undulatum (Hedw) P Beauv against Some Pathogenic Bacteria J Biol Sci2013 13 427ndash431 [CrossRef]

65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

68 Karpinski TM Adamczak A Antibacterial Activity of Ethanolic Extracts of Some Moss Species Herba Pol 2017 63 11ndash17[CrossRef]

69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

77 Nikolajeva V Liepina L Petrina Z Krumina G Grube M Muiznieks I Antibacterial Activity of Extracts from SomeBryophytes Adv Microbiol 2012 02 345ndash353 [CrossRef]

78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

79 Basile A Giordano S Sorbo S Vuotto ML Ielpo MTL Cobianchi RC Antibiotic Effects of Lunularia cruciata (Bryophyta)Extract Pharm Biol 1998 36 25ndash28 [CrossRef]

80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 2: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 2 of 21

For centuries bryophytes have been used to combat health problems in many cultureson different continents According to Indian and Chinese medicine the spectrum oftheir applications is very wide from being used to fight fevers through to treating skininfections and relieving pain [1617] Native Americans used a mixture of moss ash andhoney as a disinfectant for wounds [17] During World War I dried sphagnum mosswas used in Canada as a replacement for bandages Its effectiveness is related to its highabsorbency and bactericidal properties [18] After thorough examinations some of thespecies that were formerly considered to be therapeutic were found to be ineffective oreven in some cases toxic yet the aseptic and anti-cancer properties of numerous specieshave been confirmed They have therefore been the object of increasing scientific interestA significant number of bryophyte secondary metabolites have potential pharmacologicaleconomic or biotechnological uses The biologically active compounds that can be obtainedfrom bryophytes include antioxidants compounds toxic to specific groups of organisms(potential plant-protection agents) inhibitors of certain enzymes anti-cancer and anti-HIV-1 compounds neurotrophic compounds and compounds that relax muscles andstrengthen the heart They are also associated with numerous aromas (of carrots cedartrees mushrooms) pungency and bitterness [19] The aim of this review is to presentbryophytes as a potential source of compounds with miscellaneous possible uses and assources of materials for further promising research The paper also briefly refers to themethods of compound extraction and acquisition

Table 1 The main classes of secondary metabolites among bryophytes and their potential activities

Class

Potential Activity

Ant

ibac

teri

alan

dFu

ngic

idal

Cyt

otox

ic

Inse

ctic

idal

and

Mol

lusc

icid

al

Phyt

otox

ic

Col

d-To

lera

nt

Dro

ught

-Tol

eran

t

Ant

i-U

V

Ref

eren

ces

Benzenoids + + + [320ndash22]

Bibenzyls andbis(bibenzyls) + + + + + [319ndash24]

Fatty acidderivatives + + [320ndash25]

Flavonoids + + + [320ndash2225]

Phenylpropanoids + + + [32022ndash25]

Terpenes andterpenoids + + + + [319ndash27]

2 Ethnopharmacology

In ancient times medical utility was indicated by the appearance of a plant ie theshape and structure of its organs It was a view presented by Paracelsus as the lsquodoctrineof signaturesrsquo Following this belief the species Polytrichum commune Hedw has beenused to improve the condition of the hair Tribal cultures of South India used hair-likethallus of Frullania ericoides (Nees) Mont in a similar way The Irular tribe of the Attappadyvalleys used the thalloid gametophytes of Targionia hypophylla L to treat skin conditionsdue to its characteristic rough surface [17] The thallus of Plagiochasma appendiculatum Lehmamp Lindenb was used for skin diseases by Gaddi tribes of Himachal Pradesh India [14]American tribes used some mosses as remedies for burns the Gasuite Indians used speciesfrom the genera Philonotis (Hedw) Brid Bryum Hedw Mnium Hedw and also from theHypnaceae family while Polytrichum juniperinum Hedw was used by indigenous Alaskanand Cheyenne populations [23] Alaskan Natives also made ointment from Sphagnumleaves mixed with tallow and grease to treat cuts [28]

Agronomy 2022 12 1456 3 of 21

Pre-Columbian Mesoamerican cultures found uses for 36 species of bryophytes forceremonial craft and medical purposes [29] Some of them were mentioned in Libellus deMedicinalibus Indorum Herbis (1552)mdashthe oldest report of the medical use of bryophytesin Mesoamerica [30] Marchantia sp L was used in combination with Begonia sp L andLithanchne pauciflora (Sw) PBeauv to treat mouth sores and fever [31] Headaches weretreated by washes made of Braunia secunda (Hook) Bruch amp Schimp boiled in water [29]Tea prepared from Pleurochaete squarrosa (Brid) Lindb was used to relieve stomach acheand as a compress favoring the healing of wounds [29] The moss Sematophyllum adnatum(Michx) E Britton was used to prepare medicinal tea [18] Dendropogonella rufescens(Schimp) E Britton was used by the Zapotec community to treat the discomfort of womenafter childbirth Smoking this moss with stalk of Agave americana L and corn ear stylesgave relief for muscle and bone pain [32] Currently D rufescens is prepared as a drinkto increase the appetite for kidney and lung health and as a treatment for blindness anddiabetes-related ailments [32]

The bryophytes also have many other medical uses The liverwort Conocephalumconicum (L) Dum was used in the form of a decoction as an antibacterial antifungaland antipyretic agent It was applied to treat wounds swelling burns and snake bitesMarchantia polymorpha L was used as a medicine for inflammation liver problems bitesand cuts and as a diuretic [1633] while Frullania tamarisci (L) Dumort was utilized asan antiseptic remedy [16] Riccia L species was used to cure ringworm the fungal skininfection [28] Reboulia hemisphaerica L Raddi was used for hemostasis and to treat blotchesexternal wounds and bruises Funaria hygrometrica Hedw served as a hemostatic to curepulmonary tuberculosis hematemesis bruises and athletersquos foot dermatophytosis [33]The moss Bryum argenteum Hedw was valued as an antipyretic and antifungal medicineDue to their antimicrobial properties members of the Sphagnaceae family were used tocover wounds skin ailments and to treat eye diseases [16] During the RussondashJapaneseWar Sphagnum L mosses were used by the Japanese as a first-aid dressing on a largescale [28] Furthermore during World War I dried Sphagnum sp was used in BritainCanada and Germany as a cheap substitute for cotton bandages [1834] The aquatic mossFontinalis antipyretica Hedw boiled with beer was used as a footbath to treat chest feverfever microbial infections and for detoxication [33]

3 Secondary Metabolites

The species of bryophytes express diverse functions such as phytotoxic antibacterialantifungal insect antifeedant and molluscicidal activities [19] They can be involvedin stress tolerance ie in UV-absorptive and drought- and freezing-tolerant activities(Table 1) [319ndash26] Both extracts and isolated compounds of bryophytes are very popular instudies as sources for new applications Treatment with extracts allows examination of theactivities of all compounds contained in the plant material including their interactions [35]An important element in the preparation of extracts is the selection of appropriate solventsas this determines the extracted compounds With proper extraction methods extractsoften prove to be as effective as commercially synthesized substances

Among the known species of bryophytes biologically active compounds from differ-ent classes can be mentioned such as benzenoids bibenzyls bis(bibenzyl)s flavonoidsterpenoids phenylpropanoids and derivatives of fatty acids The spectrum of applicationof compounds contained in this group of plants is considerable as every group has atleast a few activities (Table 1) Unfortunately their use is hampered by the fact that somesubstances have not yet been identified and tested

31 Volatile Compounds

Due to the presence of oil bodies liverworts are characterized by the widest range ofaromas among bryophytes [36] The sources of odors are volatile mono- and sesquiterpenesand terpenoids as well as low-molecular weight derivatives of fatty acids or phenyl-propanoids [19] Miscellaneous pleasant fragrances with potential for use in perfumery

Agronomy 2022 12 1456 4 of 21

pharmacy and the food industry can be found in liverworts but there are also odors thatcause unpleasant sensations Some of the aromas are specific only to a single species ofliverwort Valarenzo et al [37] screened volatile metabolites in four liverwort speciesDepending on the species studied it was not possible to identify 10 to 15 of the essentialoil compounds and they require further research The unknown compounds may includemetabolites unique to bryophytes to specific families or to single species Essential oilshave also been found in mosses [38] There have been several reports that some of themshow antimicrobial activity against bacteria and fungi [39ndash41]

Unique aromas can also be found among other bryophytes eg Takakia lepidozioides SHatt amp Inoue is characterized by an aromatic blend of cinnamon and roasted wheat dueto the presence of coumarin [42] (Table 2) The smells of bryophytes depend not only oncontents of volatile secondary metabolites in their essential oils (Table 2) but also on planthabitat conditions eg Frullania species produce tamariscol (1 Figure 1) only when grownin high mountain sites [19] According to Sakurai et al [43] the aroma of the liverwortCyathodium foetidissimum Schiffn collected in Tahiti in 2016 was pleasant described aslsquonostalgicrsquo or a lsquochest of drawersrsquo in contrast to the same species found on Ua Huka inMarquesas Islands in 2009 [44] which exuded the smell of urine and feces These islandsare located in French Polynesia about 1400 km away

Table 2 Selected species of bryophytes their aromas and main volatile compounds

Species Family Major VolatileComponents 1 Odor Ref

Asterella speciesPBeauv Aytoniaceae Skatole (2) Feces-like unpleasant [45]

Conocephalum conicum(L) Dum Conocephalaceae

(ndash)-sabinene (+)-bornylacetate

methyl cinnamate (3)

Camphoraceousdistinctly mushroomy [4647]

Cyathodium foetidissimumSchiffn Cyathodiaceae

Skatole (2)bicyclogermacrene

and isolepidozene (5)lunularin (6)

Feces urine unpleasant [434849]

Frullania tamarisci(L) DumortF nepalensis

(Spreng) Lehm amp LindenbF asagrayana

Montagne

Frullaniaceae Tamariscol (1) Oak moss-like [5051]

Jungermannia obovataNees Jungermanniaceae 4-hydroxy-4-

methylcyclohex-2-en-1-one Carrot-like [1952]

Leptolejeunea ellipticaLehm amp Lindenb Lejeuneaceae p-ethylphenol (7)

p-ethyl phenyl acetate Naphtalene and dried fish [5354]

Lophocolea heterophylla(Schrad) DumortLophocolea bidentata

(L) Dumort

Lophocoleaceae (ndash)-2-methylisoborneolgeosmin (8) Strong and distinctly mossy [1955]

Mannia fragrans(Balbis) Frye et LClark Aytoniaceae Grimaldone (9) Strong sweet-mossy [5657]

Plagiochila sciophilaNees Plagiochilaceae Bicyclohumulenone (10) Sweet-mossy and woody [19]

Plagiochila rutilansLindenb Plagiochilaceae

R-pulegone (11) and severalother menthanemonoterpenoids

Peppermint-like [5859]

Symphyogyna brongniartiiMont Pallaviciniaceae Geosmin (8) Distinctly earthymusty [60]

Takakia lepidozioidesS Hatt amp Inoue Takakiaceae Coumarin (12) Cinnamon and burnt

wheat [44]

1 Bold numbers refer to the chemical structures of compounds are presented in Figure 1

Agronomy 2022 12 1456 5 of 21

Agronomy 2022 12 x FOR PEER REVIEW 5 of 21

Plagiochila rutilans Lindenb

Plagiochilaceae R-pulegone (11) and several other

menthane monoterpenoids Peppermint-like [5859]

Symphyogyna brongniartii Mont

Pallaviciniaceae Geosmin (8) Distinctly earthymusty

[60]

Takakia lepidozioides S Hatt amp Inoue

Takakiaceae Coumarin (12) Cinnamon and burnt wheat

[44]

1 Bold numbers refer to the chemical structures of compounds are presented in Figure 1

Figure 1 Chemical structures of compounds mentioned in Table 2 (1 tamariscol 2 scatole 3 methyl cinnamate 4 bicyclogermacrene 5 isolepidozene 6 lunularin 7 p-ethylphenol 8 geosmin 9 gri-maldone 10 bicyclohumulenone 11 R-pulegone 12 coumarin)

Figure 1 Chemical structures of compounds mentioned in Table 2 (1 tamariscol 2 scatole3 methyl cinnamate 4 bicyclogermacrene 5 isolepidozene 6 lunularin 7 p-ethylphenol8 geosmin 9 grimaldone 10 bicyclohumulenone 11 R-pulegone 12 coumarin)

32 Antimicrobial Compounds and Extracts

Secondary metabolites found in bryophytes such as flavonoids terpenes fatty acidderivatives bibenzyls and bis(bibenzyl)s constitute a chemical lsquobarrierrsquo against potentialpathogens justifying the use of bryophyte extracts in the folk medicine of many culturesin particular the use of bryophytes in the treatment of infections and wound cleansingResearch on bryophytes has confirmed their antimicrobial properties Table 3 presentsexamples of extracts obtained from bryophytes and the antibacterial and antifungal ac-

Agronomy 2022 12 1456 6 of 21

tivities of their extracts against selected pathogens Gram-negative bacteria show greatersensitivity to extracts obtained from bryophytes This makes them potential complementsfor antibiotics as conventional antibiotics tend to be more active against Gram-positivebacteria [1861] This phenomenon is rare in higher plants [62] The metabolites showingantibacterial activity isolated from the extracts are unique to bryophytes Among themlunularin (21) marchantin A (29) polygodial (30) riccardiphenol C (32) and sacculatal wereisolated (Table 4 Figure 2) They show activity against ie Acinetobacter calcoaceticusBacillus cereus B subtilis Cryptococcus neoformans Pseudomonas aeruginosa Salmonellatyphimurium Staphylococcus aureus and Streptococcus mutans

Table 3 Antimicrobial activities of some bryophyte extracts

Division Species Extracts Tested Bacteria Tested Fungi Ref

Bryo

phyt

a

Atrichumundulatum

(Hedw) PBeauv

Waterethanol

Bacillus mycoidesEscherichia coli

Proteus mirabilisStaphylococcus aureus

Salmonella typhii

Aspergillus fumigatusFusarium oxysporum [6364]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Bryumargenteum

HedwEthanol

Escherichia coliBacillus subtilis

Micrococcus luteusStaphilococcus aureus

Aspergillus nigerPenicillium ochrochloron

Candida albicansTrichophyton mentagrophyes

[67]

Dicranum scopariumHedw Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureusStreptococcus pyogenes

NT [68]

Fontinalis antipyreticaHedw Methanol

Escherichia coliSalmonella enteritidisShigella epidermidis

Bacillus subtilisMicrococcus flavus

Aspergillus flavusA fumigatus

A nigerPenicillium funiculosum

P ochrochloronTrichoderma viride

[69]

Hypnum cupressiformeHedw

Methanol

Bacillus subtilisEscherichia coli

Micrococcus flavusShigella enteritidis

S epidermidis

Aspergillus flavusA fumigatus

A nigerPenicillium funiculosum

P ochrochloronTrichoderma viride

[69]

Water NS Candida albicansSaccharomyces cerevisiae [70]

Plagiomniumcuspidatum

(Hedw) TJKopn-hexane

Bacillus subtilisMoraxella catarrhalis

Staphylococcus aureusShigella epidermidis

Streptococcus pyogenesS pneumonianiae

NT [71]

Agronomy 2022 12 1456 7 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Polytrichum communeHedw

Water

Escherichia coliEnterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NT [72]

Chloroformethanol

Bacillus cereusEscherichia coli

Enterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NS [73]

Polytrichumjuniperinum

Hedw

MethanolBacillus subtilis

Pseudomonas aeruginosaStaphylococcus aureus

NT [74]

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Syntrichiaruralis

(Hedw) F Weber amp DMohr

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Mar

chan

tioph

yta

Bazzania trilobata L

Dichloromethanemethanol NT

Botrytis cinereaCandida albicans

Cladosporium cucumerinumPhythophthora infestans

Pyricularia oryzaeSeptoria tritici

[75]

EthanolBacillus subtilis

Listeria monocytogenesStaphylococcus aureus

NS [76]

Frullaniadilatata

(L) Dumort

Waterethanol Staphylococcus aureus NT [77]

Lophozia ventricosa(Dicks) Dumort

Methanolethyl acetate

Bacillus cereusListeria monocytogenes

Micrococcus flavusStaphylococcus aureus

Aspergillus nigerA fumigatesA ochraceusA versicolor

Penicillium funiculosumP ochrochloron

Trichoderma viride

[78]

Agronomy 2022 12 1456 8 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Lunulariacruciata

(L) Lindb

Acetonechloroform

ethanolmethanol

water

Agrobacterium tumefaciensStaphylococcus aureusShigella epidermidis

Streptococcus faecalisProteus mirabilis

P vulgarisPseudomonas aeruginosa

Escherichia coliSalmonella typhi

Klebsiella pneumoniaeEnterobacter cloacae

E aerogenesCitrobacter diversus

Bacillus subtilisXanthomonas phoseoliErwinia chrysanthemi

NS [7980]

Marchantia polymorphaL

Chloroformmethanol

Escherichia coliStaphylococcus aureus

Proteus mirabilisPasturella multocidaXanthomonas oryzae

Candida albicansFusarium oxysporum

Rhizoctonia solaniSclerotium rolfsii

Trichophyton mentagrohtytesTilletia indica

[8182]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Porellaarboris-vitae

(With) Grolle

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

Pichia anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[83]

RebouliaHemisphaerica(L)

RaddiMethanol

Bacillus cereus B subtilisEscherichia coli

Enterococcus faecalisPseudomonas aeruginosa

Staphylococcus aureus

Aspergillus nigerPenicillium notatum [84]

Scapania asperaM Bernet amp Bernet

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

P anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[61]

Targioniahypophylla L Methanol

Bacillus substilisEscherichia coli

Staphylococcus aureus

Aspergillus nigerBotrytis cinerea

Penicillium chrysogenumP expansum

Trichoderma viridae

[8586]

Distillation NTmdashnot tested NSmdashnot shown

Agronomy 2022 12 1456 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)Nees Dumortieraceae Pseudomonas aeruginosa (MIC

64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC125 microgmL)

Bacillus cereus (125 microgmL)Bacillus megaterium (MIC

25 microgmL)Bacillus subtilis (MIC25 microgmL)

Cryptococcus neoformans (MIC125 microgmL) Staphylococcus aureus

(MIC 313ndash25)Salmonella typhimurium (MIC

100 microgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50100 microgmL) [19]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae Streptococcus mutans (LD50

8 microgmL) [19]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdashminimuminhibitory concentration Bold numbers refer to the chemical structures o Bold numbers refer to the chemicalstructures of compounds are presented in Figures 1 and 2

Agronomy 2022 12 x FOR PEER REVIEW 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)

Nees Dumortieraceae Pseudomonas aeruginosa (MIC 64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC 125 μgmL)

Bacillus cereus (125 μgmL)

Bacillus megaterium (MIC 25 μgmL)

Bacillus subtilis (MIC25 μgmL)

Cryptococcus neoformans (MIC 125 μgmL)

Staphylococcus aureus (MIC 313ndash25)

Salmonella typhimurium (MIC 100 μgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50 100 μgmL) [19]

Sacculatal (15) Pellia endiviifolia (Dicks)

Dumort Pelliaceae Streptococcus mutans (LD50 8 μgmL) [19]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdash

minimum inhibitory concentration Bold numbers refer to the chemical structures o Bold numbers

refer to the chemical structures of compounds are presented in Figures 1 and 2

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygo-

dial 15 sacculatal 16 riccardiphenol C)

Apart from their antibacterial potential bryophyte extracts show antifungal proper-

ties The results of the research show that the extracts of certain species of mosses and

liverworts do not exhibit these properties despite their antibacterial effects [737980]

Such selectivity may have industrial or medical applications [4791ndash93] On the other

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygodial15 sacculatal 16 riccardiphenol C)

Agronomy 2022 12 1456 10 of 21

Apart from their antibacterial potential bryophyte extracts show antifungal proper-ties The results of the research show that the extracts of certain species of mosses andliverworts do not exhibit these properties despite their antibacterial effects [737980] Suchselectivity may have industrial or medical applications [4791ndash93] On the other hand theisolated antifungal substances show activity against numerous pathogenic fungi (Table 5Figure 3) [7588ndash9094ndash97]

Table 5 Antifungal activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Asterelin A (17 R=H)Asterelin B (18 R=Me)

Asterella angusta(Stephani) Pandeacute KPSrivast amp Sultan Khan

Aytoniaceae Candida albicans [94]

Bazzanin B (19 R=Cl)Bazzanin S (20 R=H) Bazzania trilobata L Lepidoziaceae

Botrytis cinerea (IC50 189)Cladosporium cucumerinum (IC50

175)Pyricularia oryzae (IC50 39)

Zymoseptoria tritici (IC50 235)

[75]

Isoplagiochin D (21)Bazzania trilobata LLepidozia incurvata

LindenbLepidoziaceae Zymoseptoria tritici (IC50 159) [95]

Isoriccardin C (22)Plagiochasmaintermedium

Lindenb amp GottscheAytoniaceae Candida albicans [95]

Gymnomitrol (23)Bazzania trilobata L

Gymnomitrion obtusum(Lindb) Pears

LepidoziaceaeGymnomitriaceae

Phytophthora infestansPyricularia oryzae

Zymoseptoria tritici[7598]

Marchantin A (13) Marchantia species L Marchantiaceae

Aspergillus niger (MIC25-100 microgmL)

Pyricularia oryzae (MIC125 microgmL)

Rhizoctonia solani (MIC 50 microgmL)Saccharomyces cerevisiae (MIC

313 microgmL)Trichophyton mentagrophytes (MIC

313 microgmL)

[8889]

Marchantin H (24)

Marchantia polymorphaL

Plagiochasmaintermedium Lindenb amp

Gotische

MarchantiaceaAytoniaceae Candida albicans (MIC 256 microgmL) [97]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorphaL Marchantiaceae Candida albicans [96]

Riccardin C (27)

Asterella angusta(Stephani) Pandeacute KP

Sri-vast amp Sultan KhanPlagiochasma

intermedium Lindenb ampGotische

AytoniaceaeAytoniaceae Candida albicans [97]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Candida albicans

Trichophyton mtagropbytes [90]

IC50 the concentration of a drug that is required for 50 inhibition in vitro MICmdashminimum inhibitory concentra-tion Bold numbers refer to the chemical structures o Bold numbers refer to the chemical structures of compoundsare presented in Figures 2 and 3

Agronomy 2022 12 1456 11 of 21Agronomy 2022 12 x FOR PEER REVIEW 11 of 21

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 asterelin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardin C 23 gym-nomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH 27 riccardin C)

33 Cytotoxic Compounds The bryophyte extracts apart from their antimicrobial activities showed cytotoxic

activities in vitro [387] The same was corroborated for some particular compounds Some of them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 aster-elin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardinC 23 gymnomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH27 riccardin C)

33 Cytotoxic Compounds

The bryophyte extracts apart from their antimicrobial activities showed cytotoxicactivities in vitro [387] The same was corroborated for some particular compounds Someof them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Agronomy 2022 12 1456 12 of 21

PC3 These compounds were tested on several human and mouse tumor lines breast cancerMCF-7 cellosaurus P388 chemoresistant prostate cancer PC3 glioblastoma multiforme U-251 leukemia HL-60 liver cancer HepG2 melanoma RPMI-7951 and monocytic leukemiaU937 (Table 6 Figure 4)

Table 6 Cytotoxic compounds isolated from bryophytes with modern uses

Compounds Species Family Activity Against Ref

Jungermannenone A(28 R=OH)

Jungermannenone B(29 R=H)

Jungermannia species L Jungermanniaceae

Human leukemia HL-60 cells(JA IC50

1 13 microM)PC3 (JA 15 micromolL JB

5 micromolL)

[399]

Lunularin (6) Dumortiera hirsuta (Sw)Nees Weisnerellaceae HepG2 (IC50 = 74 microgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Human MCF-7 breastcancer (IC50 40 microgmL)

chemoresistant prostate cancerPC3 cells

A375 melanoma cells(IC50 = 745ndash1197 microgmL)

[3100101]

Marsupellone (30) Marsupella emarginata(Ehrh) Dumort Gymnomitriaceaea P388 cancer cell line

(ID50 1 microgmL) [88]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorpha LSchistochila glaucescens

(Hook) AEvans

MarchantiaceaeSchistochilaceae P388 cell line (IC50 8ndash18 microgmL) [102]

Pallidisetin A (31)Pallidisetin B (32)

Polytrichum pallidisetumFunck Polytrichaceae

Melanoma (RPMI-7951)Glioblastoma multiforme

(U-251)[103]

Plagiochin E (33) Plagiochasm intermediumLindenb amp Gottsche Aytoniaceae Chemoresistant prostate cancer

PC3 cells (IC50 599 micromolL) [100]

Riccardin C (27)

Plagiochasma intermediumLindenb amp Gottsche

Reboulia hemisphaerica (L)Raddi

Aytoniaceae Chemoresistant prostate cancerPC3 cells (IC50 322 micromolL) [100104]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae BSC cells [90]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae

Human melanoma(IC50 2ndash4 micromolL) Lu1

(IC50 57 micromolL)KB (IC50 32 micromolL)

LNCaP and ZR-75-1 cells(IC50 76 micromolL)

[105]

Trewiasine (34)

Isothecium subdiversiformeBroth

Thamnobryum sandeiBesch

BrachytheciaceaeNeckeraceae

U937 cells ascitic tumors S180hepatoma U14 solid tumor

Lewis lung carcinoma[106]

1 IC50 the concentration of a drug that is required for 50 inhibition of cell growth in vitro Bold numbersrefer to the chemical structures o Bold numbers refer to the chemical structures of compounds are presented inFigures 3 and 4

Agronomy 2022 12 1456 13 of 21Agronomy 2022 12 x FOR PEER REVIEW 13 of 21

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenone B R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds In several species of the Radula Dumort genus cannabinoid compounds have been

discovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated from Radula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor) Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests on mouse brains showed that this compound is bioavailable and selectively binds to CB1 and CB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to Δ9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenoneB R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds

In several species of the Radula Dumort genus cannabinoid compounds have beendiscovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated fromRadula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor)Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests onmouse brains showed that this compound is bioavailable and selectively binds to CB1 andCB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to ∆9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

References1 Cole TCH Hilger HH Goffinet B Bryophyte Phylogeny Poster (BPP) PeerJ Prepr 2019 7 e27571v3 [CrossRef]2 de Sousa F Foster PG Donoghue PCJ Schneider H Cox CJ Nuclear Protein Phylogenies Support the Monophyly of the

Three Bryophyte Groups (Bryophyta Schimp) New Phytol 2019 222 565ndash575 [CrossRef]

Agronomy 2022 12 1456 16 of 21

3 Asakawa Y Ludwiczuk A Nagashima F Chemical Constituents of Bryophytes Bio-and Chemical Diversity Biological Activityand Chemosystematics In Progress in the Chemistry of Organic Natural Products Springer Vienna Austria 2013 Volume 95pp 1ndash796 ISBN 9783709110843

4 Tuba Z Slack NG Stark LR (Eds) Bryophyte Ecology and Climate Change Cambridge University Press Cambridge UK 2011ISBN 978-0-521-75777-5

5 Frahm JP Manual of Topical Bryology Trop Bryol 2003 23 196 [CrossRef]6 Costa DP Nadal F da Rocha TC The First Botanical Explorations of Bryophyte Diversity in the Brazilian Amazon Mountains

High Species Diversity Low Endemism and Low Similarity Biodivers Conserv 2020 29 2663ndash2688 [CrossRef]7 Cannone N Convey P Guglielmin M Diversity Trends of Bryophytes in Continental Antarctica Polar Biol 2013 36 259ndash271

[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

Change In Photosynthesis in Bryophytes and Early Land Plants Hanson DT Rice SK Eds Springer Dordrecht The Netherlands2014 pp 309ndash324 ISBN 978-94-007-6988-5

9 Smith RJ Stark LR Habitat vs Dispersal Constraints on Bryophyte Diversity in the Mojave Desert USA J Arid Environ 2014102 76ndash81 [CrossRef]

10 Stark LR Bisexuality as an Adaptation in Desert Mosses Am Midl Nat 1983 110 445ndash448 [CrossRef]11 Scott GAM Desert Bryophytes In Bryophyte Ecology Smith AJE Ed Springer Dordrecht The Netherlands 1982 pp 105ndash122

ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

39 587ndash596 [CrossRef]14 Ren H Wang F Ye W Zhang Q Han T Huang Y Chu G Hui D Guo Q Bryophyte Diversity Is Related to Vascular

Plant Diversity and Microhabitat under Disturbance in Karst Caves Ecol Indic 2021 120 106947 [CrossRef]15 Von Reuszlig SH Koumlnig WA Olefinic Isothiocyanates and Iminodithiocarbonates from the Liverwort Corsinia coriandrina Eur J

Org Chem 2005 2005 1184ndash1188 [CrossRef]16 Chandra S Chandra D Barh A Pankaj Pandey RK Sharma IP Bryophytes Hoard of Remedies an Ethno-Medicinal

Review J Tradit Complement Med 2016 7 94ndash98 [CrossRef] [PubMed]17 Krishnan VGM Pradeep DP Aswathy JM Krishnan R Lubaina AS Murugan K Wonder Herbals-Bryophytes of

the Ponmudi Hills of Southern Western Ghats Window Into the Need for Conservation World J Pharm Pharm Sci 2014 31548ndash1562

18 Glime J Medical Uses Medical Conditions In Bryophyte Ecology Michigan Technological University Houghton MI USA 2017p 5 Available online httpsdigitalcommonsmtueduoabooks4 (accessed on 6 October 2021)

19 Asakawa Y Biologically Active Compounds from Bryophytes Pure Appl Chem 2007 79 557ndash580 [CrossRef]20 Xie CF Lou HX Secondary Metabolites in Bryophytes An Ecological Aspect Chem Biodivers 2009 6 303ndash312 [CrossRef]21 Asakawa Y Ludwiczuk A Novakovic M Bukvicki D Anchang KY Bis-Bibenzyls Bibenzyls and Terpenoids in 33 Genera

of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

Austria 1982 pp 1ndash28523 Sabovljevic MS Sabovljevic AD Ikram NKK Peramuna A Bae H Simonsen HT BryophytesmdashAn Emerging Source for

Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

110649 [CrossRef]27 Zhu MZ Li Y Zhou JC Lu JH Zhu RX Qiao YN Zhang JZ Zong Y Wang X Jin XY et al Terpenoids from

the Chinese Liverwort Odontoschisma Grosseverrucosum and Their Antifungal Virulence Activity Phytochemistry 2020 174[CrossRef]

28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

41ndash49 [CrossRef]

Agronomy 2022 12 1456 17 of 21

35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

37 Valarezo E Tandazo O Galaacuten K Rosales J Beniacutetez Aacute Volatile Metabolites in Liverworts of Ecuador Metabolites 2020 10 92[CrossRef]

38 Saritas Y Sonwa MM Iznaguen H Koumlnig WA Muhle H Mues R Volatile Constituents in Mosses (Musci) Phytochemistry2001 57 443ndash457 [CrossRef]

39 Tosun G Yaylı B Oumlzdemir T Batan N Bozdeveci A Yaylı N Volatiles and Antimicrobial Activity of the Essential Oils ofthe Mosses Pseudoscleropodium purum Eurhynchium striatum and Eurhynchium angustirete Grown in Turkey Rec Nat Prod 2015 9237ndash242

40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

43 Sakurai K Tomiyama K Kawakami Y Yaguchi Y Asakawa Y Characteristic Scent from the Tahitian Liverwort CyathodiumFoetidissimum J Oleo Sci 2018 67 1265ndash1269 [CrossRef]

44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

45 Asakawa Y Joulain D Chemical Constituents of Unidentified Malaysian Liverwort Astrella () Species J Hattori Bot Lab 1995188 183ndash188 [CrossRef]

46 Toyota M Saito T Matsunami J Asakawa Y A Comparative Study on Three Chemo-Types of the Liverwort ConocephalumConicum Using Volatile Constituents Phytochemistry 1997 44 1265ndash1270 [CrossRef]

47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

48 Ludwiczuk A Komala I Pham A Bianchini JP Raharivelomanana P Asakawa Y Volatile Components from SelectedTahitian Liverworts Nat Prod Commun 2009 4 1387ndash1392 [CrossRef]

49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

51 Pannequin A Tintaru A Desjobert JM Costa J Muselli A New Advances in the Volatile Metabolites of Frullania tamarisciFlavour Fragr J 2017 32 409ndash418 [CrossRef]

52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

64 Vats S Alam A Antibacterial Activity of Atrichum undulatum (Hedw) P Beauv against Some Pathogenic Bacteria J Biol Sci2013 13 427ndash431 [CrossRef]

65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

68 Karpinski TM Adamczak A Antibacterial Activity of Ethanolic Extracts of Some Moss Species Herba Pol 2017 63 11ndash17[CrossRef]

69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

77 Nikolajeva V Liepina L Petrina Z Krumina G Grube M Muiznieks I Antibacterial Activity of Extracts from SomeBryophytes Adv Microbiol 2012 02 345ndash353 [CrossRef]

78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

79 Basile A Giordano S Sorbo S Vuotto ML Ielpo MTL Cobianchi RC Antibiotic Effects of Lunularia cruciata (Bryophyta)Extract Pharm Biol 1998 36 25ndash28 [CrossRef]

80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 3: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 3 of 21

Pre-Columbian Mesoamerican cultures found uses for 36 species of bryophytes forceremonial craft and medical purposes [29] Some of them were mentioned in Libellus deMedicinalibus Indorum Herbis (1552)mdashthe oldest report of the medical use of bryophytesin Mesoamerica [30] Marchantia sp L was used in combination with Begonia sp L andLithanchne pauciflora (Sw) PBeauv to treat mouth sores and fever [31] Headaches weretreated by washes made of Braunia secunda (Hook) Bruch amp Schimp boiled in water [29]Tea prepared from Pleurochaete squarrosa (Brid) Lindb was used to relieve stomach acheand as a compress favoring the healing of wounds [29] The moss Sematophyllum adnatum(Michx) E Britton was used to prepare medicinal tea [18] Dendropogonella rufescens(Schimp) E Britton was used by the Zapotec community to treat the discomfort of womenafter childbirth Smoking this moss with stalk of Agave americana L and corn ear stylesgave relief for muscle and bone pain [32] Currently D rufescens is prepared as a drinkto increase the appetite for kidney and lung health and as a treatment for blindness anddiabetes-related ailments [32]

The bryophytes also have many other medical uses The liverwort Conocephalumconicum (L) Dum was used in the form of a decoction as an antibacterial antifungaland antipyretic agent It was applied to treat wounds swelling burns and snake bitesMarchantia polymorpha L was used as a medicine for inflammation liver problems bitesand cuts and as a diuretic [1633] while Frullania tamarisci (L) Dumort was utilized asan antiseptic remedy [16] Riccia L species was used to cure ringworm the fungal skininfection [28] Reboulia hemisphaerica L Raddi was used for hemostasis and to treat blotchesexternal wounds and bruises Funaria hygrometrica Hedw served as a hemostatic to curepulmonary tuberculosis hematemesis bruises and athletersquos foot dermatophytosis [33]The moss Bryum argenteum Hedw was valued as an antipyretic and antifungal medicineDue to their antimicrobial properties members of the Sphagnaceae family were used tocover wounds skin ailments and to treat eye diseases [16] During the RussondashJapaneseWar Sphagnum L mosses were used by the Japanese as a first-aid dressing on a largescale [28] Furthermore during World War I dried Sphagnum sp was used in BritainCanada and Germany as a cheap substitute for cotton bandages [1834] The aquatic mossFontinalis antipyretica Hedw boiled with beer was used as a footbath to treat chest feverfever microbial infections and for detoxication [33]

3 Secondary Metabolites

The species of bryophytes express diverse functions such as phytotoxic antibacterialantifungal insect antifeedant and molluscicidal activities [19] They can be involvedin stress tolerance ie in UV-absorptive and drought- and freezing-tolerant activities(Table 1) [319ndash26] Both extracts and isolated compounds of bryophytes are very popular instudies as sources for new applications Treatment with extracts allows examination of theactivities of all compounds contained in the plant material including their interactions [35]An important element in the preparation of extracts is the selection of appropriate solventsas this determines the extracted compounds With proper extraction methods extractsoften prove to be as effective as commercially synthesized substances

Among the known species of bryophytes biologically active compounds from differ-ent classes can be mentioned such as benzenoids bibenzyls bis(bibenzyl)s flavonoidsterpenoids phenylpropanoids and derivatives of fatty acids The spectrum of applicationof compounds contained in this group of plants is considerable as every group has atleast a few activities (Table 1) Unfortunately their use is hampered by the fact that somesubstances have not yet been identified and tested

31 Volatile Compounds

Due to the presence of oil bodies liverworts are characterized by the widest range ofaromas among bryophytes [36] The sources of odors are volatile mono- and sesquiterpenesand terpenoids as well as low-molecular weight derivatives of fatty acids or phenyl-propanoids [19] Miscellaneous pleasant fragrances with potential for use in perfumery

Agronomy 2022 12 1456 4 of 21

pharmacy and the food industry can be found in liverworts but there are also odors thatcause unpleasant sensations Some of the aromas are specific only to a single species ofliverwort Valarenzo et al [37] screened volatile metabolites in four liverwort speciesDepending on the species studied it was not possible to identify 10 to 15 of the essentialoil compounds and they require further research The unknown compounds may includemetabolites unique to bryophytes to specific families or to single species Essential oilshave also been found in mosses [38] There have been several reports that some of themshow antimicrobial activity against bacteria and fungi [39ndash41]

Unique aromas can also be found among other bryophytes eg Takakia lepidozioides SHatt amp Inoue is characterized by an aromatic blend of cinnamon and roasted wheat dueto the presence of coumarin [42] (Table 2) The smells of bryophytes depend not only oncontents of volatile secondary metabolites in their essential oils (Table 2) but also on planthabitat conditions eg Frullania species produce tamariscol (1 Figure 1) only when grownin high mountain sites [19] According to Sakurai et al [43] the aroma of the liverwortCyathodium foetidissimum Schiffn collected in Tahiti in 2016 was pleasant described aslsquonostalgicrsquo or a lsquochest of drawersrsquo in contrast to the same species found on Ua Huka inMarquesas Islands in 2009 [44] which exuded the smell of urine and feces These islandsare located in French Polynesia about 1400 km away

Table 2 Selected species of bryophytes their aromas and main volatile compounds

Species Family Major VolatileComponents 1 Odor Ref

Asterella speciesPBeauv Aytoniaceae Skatole (2) Feces-like unpleasant [45]

Conocephalum conicum(L) Dum Conocephalaceae

(ndash)-sabinene (+)-bornylacetate

methyl cinnamate (3)

Camphoraceousdistinctly mushroomy [4647]

Cyathodium foetidissimumSchiffn Cyathodiaceae

Skatole (2)bicyclogermacrene

and isolepidozene (5)lunularin (6)

Feces urine unpleasant [434849]

Frullania tamarisci(L) DumortF nepalensis

(Spreng) Lehm amp LindenbF asagrayana

Montagne

Frullaniaceae Tamariscol (1) Oak moss-like [5051]

Jungermannia obovataNees Jungermanniaceae 4-hydroxy-4-

methylcyclohex-2-en-1-one Carrot-like [1952]

Leptolejeunea ellipticaLehm amp Lindenb Lejeuneaceae p-ethylphenol (7)

p-ethyl phenyl acetate Naphtalene and dried fish [5354]

Lophocolea heterophylla(Schrad) DumortLophocolea bidentata

(L) Dumort

Lophocoleaceae (ndash)-2-methylisoborneolgeosmin (8) Strong and distinctly mossy [1955]

Mannia fragrans(Balbis) Frye et LClark Aytoniaceae Grimaldone (9) Strong sweet-mossy [5657]

Plagiochila sciophilaNees Plagiochilaceae Bicyclohumulenone (10) Sweet-mossy and woody [19]

Plagiochila rutilansLindenb Plagiochilaceae

R-pulegone (11) and severalother menthanemonoterpenoids

Peppermint-like [5859]

Symphyogyna brongniartiiMont Pallaviciniaceae Geosmin (8) Distinctly earthymusty [60]

Takakia lepidozioidesS Hatt amp Inoue Takakiaceae Coumarin (12) Cinnamon and burnt

wheat [44]

1 Bold numbers refer to the chemical structures of compounds are presented in Figure 1

Agronomy 2022 12 1456 5 of 21

Agronomy 2022 12 x FOR PEER REVIEW 5 of 21

Plagiochila rutilans Lindenb

Plagiochilaceae R-pulegone (11) and several other

menthane monoterpenoids Peppermint-like [5859]

Symphyogyna brongniartii Mont

Pallaviciniaceae Geosmin (8) Distinctly earthymusty

[60]

Takakia lepidozioides S Hatt amp Inoue

Takakiaceae Coumarin (12) Cinnamon and burnt wheat

[44]

1 Bold numbers refer to the chemical structures of compounds are presented in Figure 1

Figure 1 Chemical structures of compounds mentioned in Table 2 (1 tamariscol 2 scatole 3 methyl cinnamate 4 bicyclogermacrene 5 isolepidozene 6 lunularin 7 p-ethylphenol 8 geosmin 9 gri-maldone 10 bicyclohumulenone 11 R-pulegone 12 coumarin)

Figure 1 Chemical structures of compounds mentioned in Table 2 (1 tamariscol 2 scatole3 methyl cinnamate 4 bicyclogermacrene 5 isolepidozene 6 lunularin 7 p-ethylphenol8 geosmin 9 grimaldone 10 bicyclohumulenone 11 R-pulegone 12 coumarin)

32 Antimicrobial Compounds and Extracts

Secondary metabolites found in bryophytes such as flavonoids terpenes fatty acidderivatives bibenzyls and bis(bibenzyl)s constitute a chemical lsquobarrierrsquo against potentialpathogens justifying the use of bryophyte extracts in the folk medicine of many culturesin particular the use of bryophytes in the treatment of infections and wound cleansingResearch on bryophytes has confirmed their antimicrobial properties Table 3 presentsexamples of extracts obtained from bryophytes and the antibacterial and antifungal ac-

Agronomy 2022 12 1456 6 of 21

tivities of their extracts against selected pathogens Gram-negative bacteria show greatersensitivity to extracts obtained from bryophytes This makes them potential complementsfor antibiotics as conventional antibiotics tend to be more active against Gram-positivebacteria [1861] This phenomenon is rare in higher plants [62] The metabolites showingantibacterial activity isolated from the extracts are unique to bryophytes Among themlunularin (21) marchantin A (29) polygodial (30) riccardiphenol C (32) and sacculatal wereisolated (Table 4 Figure 2) They show activity against ie Acinetobacter calcoaceticusBacillus cereus B subtilis Cryptococcus neoformans Pseudomonas aeruginosa Salmonellatyphimurium Staphylococcus aureus and Streptococcus mutans

Table 3 Antimicrobial activities of some bryophyte extracts

Division Species Extracts Tested Bacteria Tested Fungi Ref

Bryo

phyt

a

Atrichumundulatum

(Hedw) PBeauv

Waterethanol

Bacillus mycoidesEscherichia coli

Proteus mirabilisStaphylococcus aureus

Salmonella typhii

Aspergillus fumigatusFusarium oxysporum [6364]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Bryumargenteum

HedwEthanol

Escherichia coliBacillus subtilis

Micrococcus luteusStaphilococcus aureus

Aspergillus nigerPenicillium ochrochloron

Candida albicansTrichophyton mentagrophyes

[67]

Dicranum scopariumHedw Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureusStreptococcus pyogenes

NT [68]

Fontinalis antipyreticaHedw Methanol

Escherichia coliSalmonella enteritidisShigella epidermidis

Bacillus subtilisMicrococcus flavus

Aspergillus flavusA fumigatus

A nigerPenicillium funiculosum

P ochrochloronTrichoderma viride

[69]

Hypnum cupressiformeHedw

Methanol

Bacillus subtilisEscherichia coli

Micrococcus flavusShigella enteritidis

S epidermidis

Aspergillus flavusA fumigatus

A nigerPenicillium funiculosum

P ochrochloronTrichoderma viride

[69]

Water NS Candida albicansSaccharomyces cerevisiae [70]

Plagiomniumcuspidatum

(Hedw) TJKopn-hexane

Bacillus subtilisMoraxella catarrhalis

Staphylococcus aureusShigella epidermidis

Streptococcus pyogenesS pneumonianiae

NT [71]

Agronomy 2022 12 1456 7 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Polytrichum communeHedw

Water

Escherichia coliEnterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NT [72]

Chloroformethanol

Bacillus cereusEscherichia coli

Enterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NS [73]

Polytrichumjuniperinum

Hedw

MethanolBacillus subtilis

Pseudomonas aeruginosaStaphylococcus aureus

NT [74]

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Syntrichiaruralis

(Hedw) F Weber amp DMohr

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Mar

chan

tioph

yta

Bazzania trilobata L

Dichloromethanemethanol NT

Botrytis cinereaCandida albicans

Cladosporium cucumerinumPhythophthora infestans

Pyricularia oryzaeSeptoria tritici

[75]

EthanolBacillus subtilis

Listeria monocytogenesStaphylococcus aureus

NS [76]

Frullaniadilatata

(L) Dumort

Waterethanol Staphylococcus aureus NT [77]

Lophozia ventricosa(Dicks) Dumort

Methanolethyl acetate

Bacillus cereusListeria monocytogenes

Micrococcus flavusStaphylococcus aureus

Aspergillus nigerA fumigatesA ochraceusA versicolor

Penicillium funiculosumP ochrochloron

Trichoderma viride

[78]

Agronomy 2022 12 1456 8 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Lunulariacruciata

(L) Lindb

Acetonechloroform

ethanolmethanol

water

Agrobacterium tumefaciensStaphylococcus aureusShigella epidermidis

Streptococcus faecalisProteus mirabilis

P vulgarisPseudomonas aeruginosa

Escherichia coliSalmonella typhi

Klebsiella pneumoniaeEnterobacter cloacae

E aerogenesCitrobacter diversus

Bacillus subtilisXanthomonas phoseoliErwinia chrysanthemi

NS [7980]

Marchantia polymorphaL

Chloroformmethanol

Escherichia coliStaphylococcus aureus

Proteus mirabilisPasturella multocidaXanthomonas oryzae

Candida albicansFusarium oxysporum

Rhizoctonia solaniSclerotium rolfsii

Trichophyton mentagrohtytesTilletia indica

[8182]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Porellaarboris-vitae

(With) Grolle

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

Pichia anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[83]

RebouliaHemisphaerica(L)

RaddiMethanol

Bacillus cereus B subtilisEscherichia coli

Enterococcus faecalisPseudomonas aeruginosa

Staphylococcus aureus

Aspergillus nigerPenicillium notatum [84]

Scapania asperaM Bernet amp Bernet

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

P anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[61]

Targioniahypophylla L Methanol

Bacillus substilisEscherichia coli

Staphylococcus aureus

Aspergillus nigerBotrytis cinerea

Penicillium chrysogenumP expansum

Trichoderma viridae

[8586]

Distillation NTmdashnot tested NSmdashnot shown

Agronomy 2022 12 1456 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)Nees Dumortieraceae Pseudomonas aeruginosa (MIC

64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC125 microgmL)

Bacillus cereus (125 microgmL)Bacillus megaterium (MIC

25 microgmL)Bacillus subtilis (MIC25 microgmL)

Cryptococcus neoformans (MIC125 microgmL) Staphylococcus aureus

(MIC 313ndash25)Salmonella typhimurium (MIC

100 microgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50100 microgmL) [19]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae Streptococcus mutans (LD50

8 microgmL) [19]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdashminimuminhibitory concentration Bold numbers refer to the chemical structures o Bold numbers refer to the chemicalstructures of compounds are presented in Figures 1 and 2

Agronomy 2022 12 x FOR PEER REVIEW 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)

Nees Dumortieraceae Pseudomonas aeruginosa (MIC 64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC 125 μgmL)

Bacillus cereus (125 μgmL)

Bacillus megaterium (MIC 25 μgmL)

Bacillus subtilis (MIC25 μgmL)

Cryptococcus neoformans (MIC 125 μgmL)

Staphylococcus aureus (MIC 313ndash25)

Salmonella typhimurium (MIC 100 μgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50 100 μgmL) [19]

Sacculatal (15) Pellia endiviifolia (Dicks)

Dumort Pelliaceae Streptococcus mutans (LD50 8 μgmL) [19]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdash

minimum inhibitory concentration Bold numbers refer to the chemical structures o Bold numbers

refer to the chemical structures of compounds are presented in Figures 1 and 2

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygo-

dial 15 sacculatal 16 riccardiphenol C)

Apart from their antibacterial potential bryophyte extracts show antifungal proper-

ties The results of the research show that the extracts of certain species of mosses and

liverworts do not exhibit these properties despite their antibacterial effects [737980]

Such selectivity may have industrial or medical applications [4791ndash93] On the other

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygodial15 sacculatal 16 riccardiphenol C)

Agronomy 2022 12 1456 10 of 21

Apart from their antibacterial potential bryophyte extracts show antifungal proper-ties The results of the research show that the extracts of certain species of mosses andliverworts do not exhibit these properties despite their antibacterial effects [737980] Suchselectivity may have industrial or medical applications [4791ndash93] On the other hand theisolated antifungal substances show activity against numerous pathogenic fungi (Table 5Figure 3) [7588ndash9094ndash97]

Table 5 Antifungal activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Asterelin A (17 R=H)Asterelin B (18 R=Me)

Asterella angusta(Stephani) Pandeacute KPSrivast amp Sultan Khan

Aytoniaceae Candida albicans [94]

Bazzanin B (19 R=Cl)Bazzanin S (20 R=H) Bazzania trilobata L Lepidoziaceae

Botrytis cinerea (IC50 189)Cladosporium cucumerinum (IC50

175)Pyricularia oryzae (IC50 39)

Zymoseptoria tritici (IC50 235)

[75]

Isoplagiochin D (21)Bazzania trilobata LLepidozia incurvata

LindenbLepidoziaceae Zymoseptoria tritici (IC50 159) [95]

Isoriccardin C (22)Plagiochasmaintermedium

Lindenb amp GottscheAytoniaceae Candida albicans [95]

Gymnomitrol (23)Bazzania trilobata L

Gymnomitrion obtusum(Lindb) Pears

LepidoziaceaeGymnomitriaceae

Phytophthora infestansPyricularia oryzae

Zymoseptoria tritici[7598]

Marchantin A (13) Marchantia species L Marchantiaceae

Aspergillus niger (MIC25-100 microgmL)

Pyricularia oryzae (MIC125 microgmL)

Rhizoctonia solani (MIC 50 microgmL)Saccharomyces cerevisiae (MIC

313 microgmL)Trichophyton mentagrophytes (MIC

313 microgmL)

[8889]

Marchantin H (24)

Marchantia polymorphaL

Plagiochasmaintermedium Lindenb amp

Gotische

MarchantiaceaAytoniaceae Candida albicans (MIC 256 microgmL) [97]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorphaL Marchantiaceae Candida albicans [96]

Riccardin C (27)

Asterella angusta(Stephani) Pandeacute KP

Sri-vast amp Sultan KhanPlagiochasma

intermedium Lindenb ampGotische

AytoniaceaeAytoniaceae Candida albicans [97]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Candida albicans

Trichophyton mtagropbytes [90]

IC50 the concentration of a drug that is required for 50 inhibition in vitro MICmdashminimum inhibitory concentra-tion Bold numbers refer to the chemical structures o Bold numbers refer to the chemical structures of compoundsare presented in Figures 2 and 3

Agronomy 2022 12 1456 11 of 21Agronomy 2022 12 x FOR PEER REVIEW 11 of 21

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 asterelin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardin C 23 gym-nomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH 27 riccardin C)

33 Cytotoxic Compounds The bryophyte extracts apart from their antimicrobial activities showed cytotoxic

activities in vitro [387] The same was corroborated for some particular compounds Some of them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 aster-elin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardinC 23 gymnomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH27 riccardin C)

33 Cytotoxic Compounds

The bryophyte extracts apart from their antimicrobial activities showed cytotoxicactivities in vitro [387] The same was corroborated for some particular compounds Someof them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Agronomy 2022 12 1456 12 of 21

PC3 These compounds were tested on several human and mouse tumor lines breast cancerMCF-7 cellosaurus P388 chemoresistant prostate cancer PC3 glioblastoma multiforme U-251 leukemia HL-60 liver cancer HepG2 melanoma RPMI-7951 and monocytic leukemiaU937 (Table 6 Figure 4)

Table 6 Cytotoxic compounds isolated from bryophytes with modern uses

Compounds Species Family Activity Against Ref

Jungermannenone A(28 R=OH)

Jungermannenone B(29 R=H)

Jungermannia species L Jungermanniaceae

Human leukemia HL-60 cells(JA IC50

1 13 microM)PC3 (JA 15 micromolL JB

5 micromolL)

[399]

Lunularin (6) Dumortiera hirsuta (Sw)Nees Weisnerellaceae HepG2 (IC50 = 74 microgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Human MCF-7 breastcancer (IC50 40 microgmL)

chemoresistant prostate cancerPC3 cells

A375 melanoma cells(IC50 = 745ndash1197 microgmL)

[3100101]

Marsupellone (30) Marsupella emarginata(Ehrh) Dumort Gymnomitriaceaea P388 cancer cell line

(ID50 1 microgmL) [88]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorpha LSchistochila glaucescens

(Hook) AEvans

MarchantiaceaeSchistochilaceae P388 cell line (IC50 8ndash18 microgmL) [102]

Pallidisetin A (31)Pallidisetin B (32)

Polytrichum pallidisetumFunck Polytrichaceae

Melanoma (RPMI-7951)Glioblastoma multiforme

(U-251)[103]

Plagiochin E (33) Plagiochasm intermediumLindenb amp Gottsche Aytoniaceae Chemoresistant prostate cancer

PC3 cells (IC50 599 micromolL) [100]

Riccardin C (27)

Plagiochasma intermediumLindenb amp Gottsche

Reboulia hemisphaerica (L)Raddi

Aytoniaceae Chemoresistant prostate cancerPC3 cells (IC50 322 micromolL) [100104]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae BSC cells [90]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae

Human melanoma(IC50 2ndash4 micromolL) Lu1

(IC50 57 micromolL)KB (IC50 32 micromolL)

LNCaP and ZR-75-1 cells(IC50 76 micromolL)

[105]

Trewiasine (34)

Isothecium subdiversiformeBroth

Thamnobryum sandeiBesch

BrachytheciaceaeNeckeraceae

U937 cells ascitic tumors S180hepatoma U14 solid tumor

Lewis lung carcinoma[106]

1 IC50 the concentration of a drug that is required for 50 inhibition of cell growth in vitro Bold numbersrefer to the chemical structures o Bold numbers refer to the chemical structures of compounds are presented inFigures 3 and 4

Agronomy 2022 12 1456 13 of 21Agronomy 2022 12 x FOR PEER REVIEW 13 of 21

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenone B R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds In several species of the Radula Dumort genus cannabinoid compounds have been

discovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated from Radula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor) Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests on mouse brains showed that this compound is bioavailable and selectively binds to CB1 and CB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to Δ9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenoneB R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds

In several species of the Radula Dumort genus cannabinoid compounds have beendiscovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated fromRadula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor)Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests onmouse brains showed that this compound is bioavailable and selectively binds to CB1 andCB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to ∆9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

References1 Cole TCH Hilger HH Goffinet B Bryophyte Phylogeny Poster (BPP) PeerJ Prepr 2019 7 e27571v3 [CrossRef]2 de Sousa F Foster PG Donoghue PCJ Schneider H Cox CJ Nuclear Protein Phylogenies Support the Monophyly of the

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Agronomy 2022 12 1456 16 of 21

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High Species Diversity Low Endemism and Low Similarity Biodivers Conserv 2020 29 2663ndash2688 [CrossRef]7 Cannone N Convey P Guglielmin M Diversity Trends of Bryophytes in Continental Antarctica Polar Biol 2013 36 259ndash271

[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

Change In Photosynthesis in Bryophytes and Early Land Plants Hanson DT Rice SK Eds Springer Dordrecht The Netherlands2014 pp 309ndash324 ISBN 978-94-007-6988-5

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ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

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Plant Diversity and Microhabitat under Disturbance in Karst Caves Ecol Indic 2021 120 106947 [CrossRef]15 Von Reuszlig SH Koumlnig WA Olefinic Isothiocyanates and Iminodithiocarbonates from the Liverwort Corsinia coriandrina Eur J

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the Ponmudi Hills of Southern Western Ghats Window Into the Need for Conservation World J Pharm Pharm Sci 2014 31548ndash1562

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of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

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Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

110649 [CrossRef]27 Zhu MZ Li Y Zhou JC Lu JH Zhu RX Qiao YN Zhang JZ Zong Y Wang X Jin XY et al Terpenoids from

the Chinese Liverwort Odontoschisma Grosseverrucosum and Their Antifungal Virulence Activity Phytochemistry 2020 174[CrossRef]

28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

41ndash49 [CrossRef]

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35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

37 Valarezo E Tandazo O Galaacuten K Rosales J Beniacutetez Aacute Volatile Metabolites in Liverworts of Ecuador Metabolites 2020 10 92[CrossRef]

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39 Tosun G Yaylı B Oumlzdemir T Batan N Bozdeveci A Yaylı N Volatiles and Antimicrobial Activity of the Essential Oils ofthe Mosses Pseudoscleropodium purum Eurhynchium striatum and Eurhynchium angustirete Grown in Turkey Rec Nat Prod 2015 9237ndash242

40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

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44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

45 Asakawa Y Joulain D Chemical Constituents of Unidentified Malaysian Liverwort Astrella () Species J Hattori Bot Lab 1995188 183ndash188 [CrossRef]

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47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

48 Ludwiczuk A Komala I Pham A Bianchini JP Raharivelomanana P Asakawa Y Volatile Components from SelectedTahitian Liverworts Nat Prod Commun 2009 4 1387ndash1392 [CrossRef]

49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

51 Pannequin A Tintaru A Desjobert JM Costa J Muselli A New Advances in the Volatile Metabolites of Frullania tamarisciFlavour Fragr J 2017 32 409ndash418 [CrossRef]

52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

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65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

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69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

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78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

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80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 4: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 4 of 21

pharmacy and the food industry can be found in liverworts but there are also odors thatcause unpleasant sensations Some of the aromas are specific only to a single species ofliverwort Valarenzo et al [37] screened volatile metabolites in four liverwort speciesDepending on the species studied it was not possible to identify 10 to 15 of the essentialoil compounds and they require further research The unknown compounds may includemetabolites unique to bryophytes to specific families or to single species Essential oilshave also been found in mosses [38] There have been several reports that some of themshow antimicrobial activity against bacteria and fungi [39ndash41]

Unique aromas can also be found among other bryophytes eg Takakia lepidozioides SHatt amp Inoue is characterized by an aromatic blend of cinnamon and roasted wheat dueto the presence of coumarin [42] (Table 2) The smells of bryophytes depend not only oncontents of volatile secondary metabolites in their essential oils (Table 2) but also on planthabitat conditions eg Frullania species produce tamariscol (1 Figure 1) only when grownin high mountain sites [19] According to Sakurai et al [43] the aroma of the liverwortCyathodium foetidissimum Schiffn collected in Tahiti in 2016 was pleasant described aslsquonostalgicrsquo or a lsquochest of drawersrsquo in contrast to the same species found on Ua Huka inMarquesas Islands in 2009 [44] which exuded the smell of urine and feces These islandsare located in French Polynesia about 1400 km away

Table 2 Selected species of bryophytes their aromas and main volatile compounds

Species Family Major VolatileComponents 1 Odor Ref

Asterella speciesPBeauv Aytoniaceae Skatole (2) Feces-like unpleasant [45]

Conocephalum conicum(L) Dum Conocephalaceae

(ndash)-sabinene (+)-bornylacetate

methyl cinnamate (3)

Camphoraceousdistinctly mushroomy [4647]

Cyathodium foetidissimumSchiffn Cyathodiaceae

Skatole (2)bicyclogermacrene

and isolepidozene (5)lunularin (6)

Feces urine unpleasant [434849]

Frullania tamarisci(L) DumortF nepalensis

(Spreng) Lehm amp LindenbF asagrayana

Montagne

Frullaniaceae Tamariscol (1) Oak moss-like [5051]

Jungermannia obovataNees Jungermanniaceae 4-hydroxy-4-

methylcyclohex-2-en-1-one Carrot-like [1952]

Leptolejeunea ellipticaLehm amp Lindenb Lejeuneaceae p-ethylphenol (7)

p-ethyl phenyl acetate Naphtalene and dried fish [5354]

Lophocolea heterophylla(Schrad) DumortLophocolea bidentata

(L) Dumort

Lophocoleaceae (ndash)-2-methylisoborneolgeosmin (8) Strong and distinctly mossy [1955]

Mannia fragrans(Balbis) Frye et LClark Aytoniaceae Grimaldone (9) Strong sweet-mossy [5657]

Plagiochila sciophilaNees Plagiochilaceae Bicyclohumulenone (10) Sweet-mossy and woody [19]

Plagiochila rutilansLindenb Plagiochilaceae

R-pulegone (11) and severalother menthanemonoterpenoids

Peppermint-like [5859]

Symphyogyna brongniartiiMont Pallaviciniaceae Geosmin (8) Distinctly earthymusty [60]

Takakia lepidozioidesS Hatt amp Inoue Takakiaceae Coumarin (12) Cinnamon and burnt

wheat [44]

1 Bold numbers refer to the chemical structures of compounds are presented in Figure 1

Agronomy 2022 12 1456 5 of 21

Agronomy 2022 12 x FOR PEER REVIEW 5 of 21

Plagiochila rutilans Lindenb

Plagiochilaceae R-pulegone (11) and several other

menthane monoterpenoids Peppermint-like [5859]

Symphyogyna brongniartii Mont

Pallaviciniaceae Geosmin (8) Distinctly earthymusty

[60]

Takakia lepidozioides S Hatt amp Inoue

Takakiaceae Coumarin (12) Cinnamon and burnt wheat

[44]

1 Bold numbers refer to the chemical structures of compounds are presented in Figure 1

Figure 1 Chemical structures of compounds mentioned in Table 2 (1 tamariscol 2 scatole 3 methyl cinnamate 4 bicyclogermacrene 5 isolepidozene 6 lunularin 7 p-ethylphenol 8 geosmin 9 gri-maldone 10 bicyclohumulenone 11 R-pulegone 12 coumarin)

Figure 1 Chemical structures of compounds mentioned in Table 2 (1 tamariscol 2 scatole3 methyl cinnamate 4 bicyclogermacrene 5 isolepidozene 6 lunularin 7 p-ethylphenol8 geosmin 9 grimaldone 10 bicyclohumulenone 11 R-pulegone 12 coumarin)

32 Antimicrobial Compounds and Extracts

Secondary metabolites found in bryophytes such as flavonoids terpenes fatty acidderivatives bibenzyls and bis(bibenzyl)s constitute a chemical lsquobarrierrsquo against potentialpathogens justifying the use of bryophyte extracts in the folk medicine of many culturesin particular the use of bryophytes in the treatment of infections and wound cleansingResearch on bryophytes has confirmed their antimicrobial properties Table 3 presentsexamples of extracts obtained from bryophytes and the antibacterial and antifungal ac-

Agronomy 2022 12 1456 6 of 21

tivities of their extracts against selected pathogens Gram-negative bacteria show greatersensitivity to extracts obtained from bryophytes This makes them potential complementsfor antibiotics as conventional antibiotics tend to be more active against Gram-positivebacteria [1861] This phenomenon is rare in higher plants [62] The metabolites showingantibacterial activity isolated from the extracts are unique to bryophytes Among themlunularin (21) marchantin A (29) polygodial (30) riccardiphenol C (32) and sacculatal wereisolated (Table 4 Figure 2) They show activity against ie Acinetobacter calcoaceticusBacillus cereus B subtilis Cryptococcus neoformans Pseudomonas aeruginosa Salmonellatyphimurium Staphylococcus aureus and Streptococcus mutans

Table 3 Antimicrobial activities of some bryophyte extracts

Division Species Extracts Tested Bacteria Tested Fungi Ref

Bryo

phyt

a

Atrichumundulatum

(Hedw) PBeauv

Waterethanol

Bacillus mycoidesEscherichia coli

Proteus mirabilisStaphylococcus aureus

Salmonella typhii

Aspergillus fumigatusFusarium oxysporum [6364]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Bryumargenteum

HedwEthanol

Escherichia coliBacillus subtilis

Micrococcus luteusStaphilococcus aureus

Aspergillus nigerPenicillium ochrochloron

Candida albicansTrichophyton mentagrophyes

[67]

Dicranum scopariumHedw Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureusStreptococcus pyogenes

NT [68]

Fontinalis antipyreticaHedw Methanol

Escherichia coliSalmonella enteritidisShigella epidermidis

Bacillus subtilisMicrococcus flavus

Aspergillus flavusA fumigatus

A nigerPenicillium funiculosum

P ochrochloronTrichoderma viride

[69]

Hypnum cupressiformeHedw

Methanol

Bacillus subtilisEscherichia coli

Micrococcus flavusShigella enteritidis

S epidermidis

Aspergillus flavusA fumigatus

A nigerPenicillium funiculosum

P ochrochloronTrichoderma viride

[69]

Water NS Candida albicansSaccharomyces cerevisiae [70]

Plagiomniumcuspidatum

(Hedw) TJKopn-hexane

Bacillus subtilisMoraxella catarrhalis

Staphylococcus aureusShigella epidermidis

Streptococcus pyogenesS pneumonianiae

NT [71]

Agronomy 2022 12 1456 7 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Polytrichum communeHedw

Water

Escherichia coliEnterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NT [72]

Chloroformethanol

Bacillus cereusEscherichia coli

Enterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NS [73]

Polytrichumjuniperinum

Hedw

MethanolBacillus subtilis

Pseudomonas aeruginosaStaphylococcus aureus

NT [74]

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Syntrichiaruralis

(Hedw) F Weber amp DMohr

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Mar

chan

tioph

yta

Bazzania trilobata L

Dichloromethanemethanol NT

Botrytis cinereaCandida albicans

Cladosporium cucumerinumPhythophthora infestans

Pyricularia oryzaeSeptoria tritici

[75]

EthanolBacillus subtilis

Listeria monocytogenesStaphylococcus aureus

NS [76]

Frullaniadilatata

(L) Dumort

Waterethanol Staphylococcus aureus NT [77]

Lophozia ventricosa(Dicks) Dumort

Methanolethyl acetate

Bacillus cereusListeria monocytogenes

Micrococcus flavusStaphylococcus aureus

Aspergillus nigerA fumigatesA ochraceusA versicolor

Penicillium funiculosumP ochrochloron

Trichoderma viride

[78]

Agronomy 2022 12 1456 8 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Lunulariacruciata

(L) Lindb

Acetonechloroform

ethanolmethanol

water

Agrobacterium tumefaciensStaphylococcus aureusShigella epidermidis

Streptococcus faecalisProteus mirabilis

P vulgarisPseudomonas aeruginosa

Escherichia coliSalmonella typhi

Klebsiella pneumoniaeEnterobacter cloacae

E aerogenesCitrobacter diversus

Bacillus subtilisXanthomonas phoseoliErwinia chrysanthemi

NS [7980]

Marchantia polymorphaL

Chloroformmethanol

Escherichia coliStaphylococcus aureus

Proteus mirabilisPasturella multocidaXanthomonas oryzae

Candida albicansFusarium oxysporum

Rhizoctonia solaniSclerotium rolfsii

Trichophyton mentagrohtytesTilletia indica

[8182]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Porellaarboris-vitae

(With) Grolle

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

Pichia anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[83]

RebouliaHemisphaerica(L)

RaddiMethanol

Bacillus cereus B subtilisEscherichia coli

Enterococcus faecalisPseudomonas aeruginosa

Staphylococcus aureus

Aspergillus nigerPenicillium notatum [84]

Scapania asperaM Bernet amp Bernet

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

P anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[61]

Targioniahypophylla L Methanol

Bacillus substilisEscherichia coli

Staphylococcus aureus

Aspergillus nigerBotrytis cinerea

Penicillium chrysogenumP expansum

Trichoderma viridae

[8586]

Distillation NTmdashnot tested NSmdashnot shown

Agronomy 2022 12 1456 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)Nees Dumortieraceae Pseudomonas aeruginosa (MIC

64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC125 microgmL)

Bacillus cereus (125 microgmL)Bacillus megaterium (MIC

25 microgmL)Bacillus subtilis (MIC25 microgmL)

Cryptococcus neoformans (MIC125 microgmL) Staphylococcus aureus

(MIC 313ndash25)Salmonella typhimurium (MIC

100 microgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50100 microgmL) [19]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae Streptococcus mutans (LD50

8 microgmL) [19]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdashminimuminhibitory concentration Bold numbers refer to the chemical structures o Bold numbers refer to the chemicalstructures of compounds are presented in Figures 1 and 2

Agronomy 2022 12 x FOR PEER REVIEW 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)

Nees Dumortieraceae Pseudomonas aeruginosa (MIC 64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC 125 μgmL)

Bacillus cereus (125 μgmL)

Bacillus megaterium (MIC 25 μgmL)

Bacillus subtilis (MIC25 μgmL)

Cryptococcus neoformans (MIC 125 μgmL)

Staphylococcus aureus (MIC 313ndash25)

Salmonella typhimurium (MIC 100 μgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50 100 μgmL) [19]

Sacculatal (15) Pellia endiviifolia (Dicks)

Dumort Pelliaceae Streptococcus mutans (LD50 8 μgmL) [19]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdash

minimum inhibitory concentration Bold numbers refer to the chemical structures o Bold numbers

refer to the chemical structures of compounds are presented in Figures 1 and 2

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygo-

dial 15 sacculatal 16 riccardiphenol C)

Apart from their antibacterial potential bryophyte extracts show antifungal proper-

ties The results of the research show that the extracts of certain species of mosses and

liverworts do not exhibit these properties despite their antibacterial effects [737980]

Such selectivity may have industrial or medical applications [4791ndash93] On the other

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygodial15 sacculatal 16 riccardiphenol C)

Agronomy 2022 12 1456 10 of 21

Apart from their antibacterial potential bryophyte extracts show antifungal proper-ties The results of the research show that the extracts of certain species of mosses andliverworts do not exhibit these properties despite their antibacterial effects [737980] Suchselectivity may have industrial or medical applications [4791ndash93] On the other hand theisolated antifungal substances show activity against numerous pathogenic fungi (Table 5Figure 3) [7588ndash9094ndash97]

Table 5 Antifungal activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Asterelin A (17 R=H)Asterelin B (18 R=Me)

Asterella angusta(Stephani) Pandeacute KPSrivast amp Sultan Khan

Aytoniaceae Candida albicans [94]

Bazzanin B (19 R=Cl)Bazzanin S (20 R=H) Bazzania trilobata L Lepidoziaceae

Botrytis cinerea (IC50 189)Cladosporium cucumerinum (IC50

175)Pyricularia oryzae (IC50 39)

Zymoseptoria tritici (IC50 235)

[75]

Isoplagiochin D (21)Bazzania trilobata LLepidozia incurvata

LindenbLepidoziaceae Zymoseptoria tritici (IC50 159) [95]

Isoriccardin C (22)Plagiochasmaintermedium

Lindenb amp GottscheAytoniaceae Candida albicans [95]

Gymnomitrol (23)Bazzania trilobata L

Gymnomitrion obtusum(Lindb) Pears

LepidoziaceaeGymnomitriaceae

Phytophthora infestansPyricularia oryzae

Zymoseptoria tritici[7598]

Marchantin A (13) Marchantia species L Marchantiaceae

Aspergillus niger (MIC25-100 microgmL)

Pyricularia oryzae (MIC125 microgmL)

Rhizoctonia solani (MIC 50 microgmL)Saccharomyces cerevisiae (MIC

313 microgmL)Trichophyton mentagrophytes (MIC

313 microgmL)

[8889]

Marchantin H (24)

Marchantia polymorphaL

Plagiochasmaintermedium Lindenb amp

Gotische

MarchantiaceaAytoniaceae Candida albicans (MIC 256 microgmL) [97]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorphaL Marchantiaceae Candida albicans [96]

Riccardin C (27)

Asterella angusta(Stephani) Pandeacute KP

Sri-vast amp Sultan KhanPlagiochasma

intermedium Lindenb ampGotische

AytoniaceaeAytoniaceae Candida albicans [97]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Candida albicans

Trichophyton mtagropbytes [90]

IC50 the concentration of a drug that is required for 50 inhibition in vitro MICmdashminimum inhibitory concentra-tion Bold numbers refer to the chemical structures o Bold numbers refer to the chemical structures of compoundsare presented in Figures 2 and 3

Agronomy 2022 12 1456 11 of 21Agronomy 2022 12 x FOR PEER REVIEW 11 of 21

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 asterelin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardin C 23 gym-nomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH 27 riccardin C)

33 Cytotoxic Compounds The bryophyte extracts apart from their antimicrobial activities showed cytotoxic

activities in vitro [387] The same was corroborated for some particular compounds Some of them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 aster-elin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardinC 23 gymnomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH27 riccardin C)

33 Cytotoxic Compounds

The bryophyte extracts apart from their antimicrobial activities showed cytotoxicactivities in vitro [387] The same was corroborated for some particular compounds Someof them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Agronomy 2022 12 1456 12 of 21

PC3 These compounds were tested on several human and mouse tumor lines breast cancerMCF-7 cellosaurus P388 chemoresistant prostate cancer PC3 glioblastoma multiforme U-251 leukemia HL-60 liver cancer HepG2 melanoma RPMI-7951 and monocytic leukemiaU937 (Table 6 Figure 4)

Table 6 Cytotoxic compounds isolated from bryophytes with modern uses

Compounds Species Family Activity Against Ref

Jungermannenone A(28 R=OH)

Jungermannenone B(29 R=H)

Jungermannia species L Jungermanniaceae

Human leukemia HL-60 cells(JA IC50

1 13 microM)PC3 (JA 15 micromolL JB

5 micromolL)

[399]

Lunularin (6) Dumortiera hirsuta (Sw)Nees Weisnerellaceae HepG2 (IC50 = 74 microgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Human MCF-7 breastcancer (IC50 40 microgmL)

chemoresistant prostate cancerPC3 cells

A375 melanoma cells(IC50 = 745ndash1197 microgmL)

[3100101]

Marsupellone (30) Marsupella emarginata(Ehrh) Dumort Gymnomitriaceaea P388 cancer cell line

(ID50 1 microgmL) [88]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorpha LSchistochila glaucescens

(Hook) AEvans

MarchantiaceaeSchistochilaceae P388 cell line (IC50 8ndash18 microgmL) [102]

Pallidisetin A (31)Pallidisetin B (32)

Polytrichum pallidisetumFunck Polytrichaceae

Melanoma (RPMI-7951)Glioblastoma multiforme

(U-251)[103]

Plagiochin E (33) Plagiochasm intermediumLindenb amp Gottsche Aytoniaceae Chemoresistant prostate cancer

PC3 cells (IC50 599 micromolL) [100]

Riccardin C (27)

Plagiochasma intermediumLindenb amp Gottsche

Reboulia hemisphaerica (L)Raddi

Aytoniaceae Chemoresistant prostate cancerPC3 cells (IC50 322 micromolL) [100104]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae BSC cells [90]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae

Human melanoma(IC50 2ndash4 micromolL) Lu1

(IC50 57 micromolL)KB (IC50 32 micromolL)

LNCaP and ZR-75-1 cells(IC50 76 micromolL)

[105]

Trewiasine (34)

Isothecium subdiversiformeBroth

Thamnobryum sandeiBesch

BrachytheciaceaeNeckeraceae

U937 cells ascitic tumors S180hepatoma U14 solid tumor

Lewis lung carcinoma[106]

1 IC50 the concentration of a drug that is required for 50 inhibition of cell growth in vitro Bold numbersrefer to the chemical structures o Bold numbers refer to the chemical structures of compounds are presented inFigures 3 and 4

Agronomy 2022 12 1456 13 of 21Agronomy 2022 12 x FOR PEER REVIEW 13 of 21

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenone B R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds In several species of the Radula Dumort genus cannabinoid compounds have been

discovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated from Radula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor) Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests on mouse brains showed that this compound is bioavailable and selectively binds to CB1 and CB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to Δ9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenoneB R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds

In several species of the Radula Dumort genus cannabinoid compounds have beendiscovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated fromRadula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor)Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests onmouse brains showed that this compound is bioavailable and selectively binds to CB1 andCB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to ∆9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

References1 Cole TCH Hilger HH Goffinet B Bryophyte Phylogeny Poster (BPP) PeerJ Prepr 2019 7 e27571v3 [CrossRef]2 de Sousa F Foster PG Donoghue PCJ Schneider H Cox CJ Nuclear Protein Phylogenies Support the Monophyly of the

Three Bryophyte Groups (Bryophyta Schimp) New Phytol 2019 222 565ndash575 [CrossRef]

Agronomy 2022 12 1456 16 of 21

3 Asakawa Y Ludwiczuk A Nagashima F Chemical Constituents of Bryophytes Bio-and Chemical Diversity Biological Activityand Chemosystematics In Progress in the Chemistry of Organic Natural Products Springer Vienna Austria 2013 Volume 95pp 1ndash796 ISBN 9783709110843

4 Tuba Z Slack NG Stark LR (Eds) Bryophyte Ecology and Climate Change Cambridge University Press Cambridge UK 2011ISBN 978-0-521-75777-5

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High Species Diversity Low Endemism and Low Similarity Biodivers Conserv 2020 29 2663ndash2688 [CrossRef]7 Cannone N Convey P Guglielmin M Diversity Trends of Bryophytes in Continental Antarctica Polar Biol 2013 36 259ndash271

[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

Change In Photosynthesis in Bryophytes and Early Land Plants Hanson DT Rice SK Eds Springer Dordrecht The Netherlands2014 pp 309ndash324 ISBN 978-94-007-6988-5

9 Smith RJ Stark LR Habitat vs Dispersal Constraints on Bryophyte Diversity in the Mojave Desert USA J Arid Environ 2014102 76ndash81 [CrossRef]

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ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

39 587ndash596 [CrossRef]14 Ren H Wang F Ye W Zhang Q Han T Huang Y Chu G Hui D Guo Q Bryophyte Diversity Is Related to Vascular

Plant Diversity and Microhabitat under Disturbance in Karst Caves Ecol Indic 2021 120 106947 [CrossRef]15 Von Reuszlig SH Koumlnig WA Olefinic Isothiocyanates and Iminodithiocarbonates from the Liverwort Corsinia coriandrina Eur J

Org Chem 2005 2005 1184ndash1188 [CrossRef]16 Chandra S Chandra D Barh A Pankaj Pandey RK Sharma IP Bryophytes Hoard of Remedies an Ethno-Medicinal

Review J Tradit Complement Med 2016 7 94ndash98 [CrossRef] [PubMed]17 Krishnan VGM Pradeep DP Aswathy JM Krishnan R Lubaina AS Murugan K Wonder Herbals-Bryophytes of

the Ponmudi Hills of Southern Western Ghats Window Into the Need for Conservation World J Pharm Pharm Sci 2014 31548ndash1562

18 Glime J Medical Uses Medical Conditions In Bryophyte Ecology Michigan Technological University Houghton MI USA 2017p 5 Available online httpsdigitalcommonsmtueduoabooks4 (accessed on 6 October 2021)

19 Asakawa Y Biologically Active Compounds from Bryophytes Pure Appl Chem 2007 79 557ndash580 [CrossRef]20 Xie CF Lou HX Secondary Metabolites in Bryophytes An Ecological Aspect Chem Biodivers 2009 6 303ndash312 [CrossRef]21 Asakawa Y Ludwiczuk A Novakovic M Bukvicki D Anchang KY Bis-Bibenzyls Bibenzyls and Terpenoids in 33 Genera

of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

Austria 1982 pp 1ndash28523 Sabovljevic MS Sabovljevic AD Ikram NKK Peramuna A Bae H Simonsen HT BryophytesmdashAn Emerging Source for

Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

110649 [CrossRef]27 Zhu MZ Li Y Zhou JC Lu JH Zhu RX Qiao YN Zhang JZ Zong Y Wang X Jin XY et al Terpenoids from

the Chinese Liverwort Odontoschisma Grosseverrucosum and Their Antifungal Virulence Activity Phytochemistry 2020 174[CrossRef]

28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

41ndash49 [CrossRef]

Agronomy 2022 12 1456 17 of 21

35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

37 Valarezo E Tandazo O Galaacuten K Rosales J Beniacutetez Aacute Volatile Metabolites in Liverworts of Ecuador Metabolites 2020 10 92[CrossRef]

38 Saritas Y Sonwa MM Iznaguen H Koumlnig WA Muhle H Mues R Volatile Constituents in Mosses (Musci) Phytochemistry2001 57 443ndash457 [CrossRef]

39 Tosun G Yaylı B Oumlzdemir T Batan N Bozdeveci A Yaylı N Volatiles and Antimicrobial Activity of the Essential Oils ofthe Mosses Pseudoscleropodium purum Eurhynchium striatum and Eurhynchium angustirete Grown in Turkey Rec Nat Prod 2015 9237ndash242

40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

43 Sakurai K Tomiyama K Kawakami Y Yaguchi Y Asakawa Y Characteristic Scent from the Tahitian Liverwort CyathodiumFoetidissimum J Oleo Sci 2018 67 1265ndash1269 [CrossRef]

44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

45 Asakawa Y Joulain D Chemical Constituents of Unidentified Malaysian Liverwort Astrella () Species J Hattori Bot Lab 1995188 183ndash188 [CrossRef]

46 Toyota M Saito T Matsunami J Asakawa Y A Comparative Study on Three Chemo-Types of the Liverwort ConocephalumConicum Using Volatile Constituents Phytochemistry 1997 44 1265ndash1270 [CrossRef]

47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

48 Ludwiczuk A Komala I Pham A Bianchini JP Raharivelomanana P Asakawa Y Volatile Components from SelectedTahitian Liverworts Nat Prod Commun 2009 4 1387ndash1392 [CrossRef]

49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

51 Pannequin A Tintaru A Desjobert JM Costa J Muselli A New Advances in the Volatile Metabolites of Frullania tamarisciFlavour Fragr J 2017 32 409ndash418 [CrossRef]

52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

64 Vats S Alam A Antibacterial Activity of Atrichum undulatum (Hedw) P Beauv against Some Pathogenic Bacteria J Biol Sci2013 13 427ndash431 [CrossRef]

65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

68 Karpinski TM Adamczak A Antibacterial Activity of Ethanolic Extracts of Some Moss Species Herba Pol 2017 63 11ndash17[CrossRef]

69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

77 Nikolajeva V Liepina L Petrina Z Krumina G Grube M Muiznieks I Antibacterial Activity of Extracts from SomeBryophytes Adv Microbiol 2012 02 345ndash353 [CrossRef]

78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

79 Basile A Giordano S Sorbo S Vuotto ML Ielpo MTL Cobianchi RC Antibiotic Effects of Lunularia cruciata (Bryophyta)Extract Pharm Biol 1998 36 25ndash28 [CrossRef]

80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 5: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 5 of 21

Agronomy 2022 12 x FOR PEER REVIEW 5 of 21

Plagiochila rutilans Lindenb

Plagiochilaceae R-pulegone (11) and several other

menthane monoterpenoids Peppermint-like [5859]

Symphyogyna brongniartii Mont

Pallaviciniaceae Geosmin (8) Distinctly earthymusty

[60]

Takakia lepidozioides S Hatt amp Inoue

Takakiaceae Coumarin (12) Cinnamon and burnt wheat

[44]

1 Bold numbers refer to the chemical structures of compounds are presented in Figure 1

Figure 1 Chemical structures of compounds mentioned in Table 2 (1 tamariscol 2 scatole 3 methyl cinnamate 4 bicyclogermacrene 5 isolepidozene 6 lunularin 7 p-ethylphenol 8 geosmin 9 gri-maldone 10 bicyclohumulenone 11 R-pulegone 12 coumarin)

Figure 1 Chemical structures of compounds mentioned in Table 2 (1 tamariscol 2 scatole3 methyl cinnamate 4 bicyclogermacrene 5 isolepidozene 6 lunularin 7 p-ethylphenol8 geosmin 9 grimaldone 10 bicyclohumulenone 11 R-pulegone 12 coumarin)

32 Antimicrobial Compounds and Extracts

Secondary metabolites found in bryophytes such as flavonoids terpenes fatty acidderivatives bibenzyls and bis(bibenzyl)s constitute a chemical lsquobarrierrsquo against potentialpathogens justifying the use of bryophyte extracts in the folk medicine of many culturesin particular the use of bryophytes in the treatment of infections and wound cleansingResearch on bryophytes has confirmed their antimicrobial properties Table 3 presentsexamples of extracts obtained from bryophytes and the antibacterial and antifungal ac-

Agronomy 2022 12 1456 6 of 21

tivities of their extracts against selected pathogens Gram-negative bacteria show greatersensitivity to extracts obtained from bryophytes This makes them potential complementsfor antibiotics as conventional antibiotics tend to be more active against Gram-positivebacteria [1861] This phenomenon is rare in higher plants [62] The metabolites showingantibacterial activity isolated from the extracts are unique to bryophytes Among themlunularin (21) marchantin A (29) polygodial (30) riccardiphenol C (32) and sacculatal wereisolated (Table 4 Figure 2) They show activity against ie Acinetobacter calcoaceticusBacillus cereus B subtilis Cryptococcus neoformans Pseudomonas aeruginosa Salmonellatyphimurium Staphylococcus aureus and Streptococcus mutans

Table 3 Antimicrobial activities of some bryophyte extracts

Division Species Extracts Tested Bacteria Tested Fungi Ref

Bryo

phyt

a

Atrichumundulatum

(Hedw) PBeauv

Waterethanol

Bacillus mycoidesEscherichia coli

Proteus mirabilisStaphylococcus aureus

Salmonella typhii

Aspergillus fumigatusFusarium oxysporum [6364]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Bryumargenteum

HedwEthanol

Escherichia coliBacillus subtilis

Micrococcus luteusStaphilococcus aureus

Aspergillus nigerPenicillium ochrochloron

Candida albicansTrichophyton mentagrophyes

[67]

Dicranum scopariumHedw Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureusStreptococcus pyogenes

NT [68]

Fontinalis antipyreticaHedw Methanol

Escherichia coliSalmonella enteritidisShigella epidermidis

Bacillus subtilisMicrococcus flavus

Aspergillus flavusA fumigatus

A nigerPenicillium funiculosum

P ochrochloronTrichoderma viride

[69]

Hypnum cupressiformeHedw

Methanol

Bacillus subtilisEscherichia coli

Micrococcus flavusShigella enteritidis

S epidermidis

Aspergillus flavusA fumigatus

A nigerPenicillium funiculosum

P ochrochloronTrichoderma viride

[69]

Water NS Candida albicansSaccharomyces cerevisiae [70]

Plagiomniumcuspidatum

(Hedw) TJKopn-hexane

Bacillus subtilisMoraxella catarrhalis

Staphylococcus aureusShigella epidermidis

Streptococcus pyogenesS pneumonianiae

NT [71]

Agronomy 2022 12 1456 7 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Polytrichum communeHedw

Water

Escherichia coliEnterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NT [72]

Chloroformethanol

Bacillus cereusEscherichia coli

Enterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NS [73]

Polytrichumjuniperinum

Hedw

MethanolBacillus subtilis

Pseudomonas aeruginosaStaphylococcus aureus

NT [74]

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Syntrichiaruralis

(Hedw) F Weber amp DMohr

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Mar

chan

tioph

yta

Bazzania trilobata L

Dichloromethanemethanol NT

Botrytis cinereaCandida albicans

Cladosporium cucumerinumPhythophthora infestans

Pyricularia oryzaeSeptoria tritici

[75]

EthanolBacillus subtilis

Listeria monocytogenesStaphylococcus aureus

NS [76]

Frullaniadilatata

(L) Dumort

Waterethanol Staphylococcus aureus NT [77]

Lophozia ventricosa(Dicks) Dumort

Methanolethyl acetate

Bacillus cereusListeria monocytogenes

Micrococcus flavusStaphylococcus aureus

Aspergillus nigerA fumigatesA ochraceusA versicolor

Penicillium funiculosumP ochrochloron

Trichoderma viride

[78]

Agronomy 2022 12 1456 8 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Lunulariacruciata

(L) Lindb

Acetonechloroform

ethanolmethanol

water

Agrobacterium tumefaciensStaphylococcus aureusShigella epidermidis

Streptococcus faecalisProteus mirabilis

P vulgarisPseudomonas aeruginosa

Escherichia coliSalmonella typhi

Klebsiella pneumoniaeEnterobacter cloacae

E aerogenesCitrobacter diversus

Bacillus subtilisXanthomonas phoseoliErwinia chrysanthemi

NS [7980]

Marchantia polymorphaL

Chloroformmethanol

Escherichia coliStaphylococcus aureus

Proteus mirabilisPasturella multocidaXanthomonas oryzae

Candida albicansFusarium oxysporum

Rhizoctonia solaniSclerotium rolfsii

Trichophyton mentagrohtytesTilletia indica

[8182]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Porellaarboris-vitae

(With) Grolle

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

Pichia anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[83]

RebouliaHemisphaerica(L)

RaddiMethanol

Bacillus cereus B subtilisEscherichia coli

Enterococcus faecalisPseudomonas aeruginosa

Staphylococcus aureus

Aspergillus nigerPenicillium notatum [84]

Scapania asperaM Bernet amp Bernet

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

P anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[61]

Targioniahypophylla L Methanol

Bacillus substilisEscherichia coli

Staphylococcus aureus

Aspergillus nigerBotrytis cinerea

Penicillium chrysogenumP expansum

Trichoderma viridae

[8586]

Distillation NTmdashnot tested NSmdashnot shown

Agronomy 2022 12 1456 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)Nees Dumortieraceae Pseudomonas aeruginosa (MIC

64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC125 microgmL)

Bacillus cereus (125 microgmL)Bacillus megaterium (MIC

25 microgmL)Bacillus subtilis (MIC25 microgmL)

Cryptococcus neoformans (MIC125 microgmL) Staphylococcus aureus

(MIC 313ndash25)Salmonella typhimurium (MIC

100 microgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50100 microgmL) [19]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae Streptococcus mutans (LD50

8 microgmL) [19]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdashminimuminhibitory concentration Bold numbers refer to the chemical structures o Bold numbers refer to the chemicalstructures of compounds are presented in Figures 1 and 2

Agronomy 2022 12 x FOR PEER REVIEW 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)

Nees Dumortieraceae Pseudomonas aeruginosa (MIC 64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC 125 μgmL)

Bacillus cereus (125 μgmL)

Bacillus megaterium (MIC 25 μgmL)

Bacillus subtilis (MIC25 μgmL)

Cryptococcus neoformans (MIC 125 μgmL)

Staphylococcus aureus (MIC 313ndash25)

Salmonella typhimurium (MIC 100 μgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50 100 μgmL) [19]

Sacculatal (15) Pellia endiviifolia (Dicks)

Dumort Pelliaceae Streptococcus mutans (LD50 8 μgmL) [19]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdash

minimum inhibitory concentration Bold numbers refer to the chemical structures o Bold numbers

refer to the chemical structures of compounds are presented in Figures 1 and 2

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygo-

dial 15 sacculatal 16 riccardiphenol C)

Apart from their antibacterial potential bryophyte extracts show antifungal proper-

ties The results of the research show that the extracts of certain species of mosses and

liverworts do not exhibit these properties despite their antibacterial effects [737980]

Such selectivity may have industrial or medical applications [4791ndash93] On the other

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygodial15 sacculatal 16 riccardiphenol C)

Agronomy 2022 12 1456 10 of 21

Apart from their antibacterial potential bryophyte extracts show antifungal proper-ties The results of the research show that the extracts of certain species of mosses andliverworts do not exhibit these properties despite their antibacterial effects [737980] Suchselectivity may have industrial or medical applications [4791ndash93] On the other hand theisolated antifungal substances show activity against numerous pathogenic fungi (Table 5Figure 3) [7588ndash9094ndash97]

Table 5 Antifungal activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Asterelin A (17 R=H)Asterelin B (18 R=Me)

Asterella angusta(Stephani) Pandeacute KPSrivast amp Sultan Khan

Aytoniaceae Candida albicans [94]

Bazzanin B (19 R=Cl)Bazzanin S (20 R=H) Bazzania trilobata L Lepidoziaceae

Botrytis cinerea (IC50 189)Cladosporium cucumerinum (IC50

175)Pyricularia oryzae (IC50 39)

Zymoseptoria tritici (IC50 235)

[75]

Isoplagiochin D (21)Bazzania trilobata LLepidozia incurvata

LindenbLepidoziaceae Zymoseptoria tritici (IC50 159) [95]

Isoriccardin C (22)Plagiochasmaintermedium

Lindenb amp GottscheAytoniaceae Candida albicans [95]

Gymnomitrol (23)Bazzania trilobata L

Gymnomitrion obtusum(Lindb) Pears

LepidoziaceaeGymnomitriaceae

Phytophthora infestansPyricularia oryzae

Zymoseptoria tritici[7598]

Marchantin A (13) Marchantia species L Marchantiaceae

Aspergillus niger (MIC25-100 microgmL)

Pyricularia oryzae (MIC125 microgmL)

Rhizoctonia solani (MIC 50 microgmL)Saccharomyces cerevisiae (MIC

313 microgmL)Trichophyton mentagrophytes (MIC

313 microgmL)

[8889]

Marchantin H (24)

Marchantia polymorphaL

Plagiochasmaintermedium Lindenb amp

Gotische

MarchantiaceaAytoniaceae Candida albicans (MIC 256 microgmL) [97]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorphaL Marchantiaceae Candida albicans [96]

Riccardin C (27)

Asterella angusta(Stephani) Pandeacute KP

Sri-vast amp Sultan KhanPlagiochasma

intermedium Lindenb ampGotische

AytoniaceaeAytoniaceae Candida albicans [97]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Candida albicans

Trichophyton mtagropbytes [90]

IC50 the concentration of a drug that is required for 50 inhibition in vitro MICmdashminimum inhibitory concentra-tion Bold numbers refer to the chemical structures o Bold numbers refer to the chemical structures of compoundsare presented in Figures 2 and 3

Agronomy 2022 12 1456 11 of 21Agronomy 2022 12 x FOR PEER REVIEW 11 of 21

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 asterelin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardin C 23 gym-nomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH 27 riccardin C)

33 Cytotoxic Compounds The bryophyte extracts apart from their antimicrobial activities showed cytotoxic

activities in vitro [387] The same was corroborated for some particular compounds Some of them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 aster-elin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardinC 23 gymnomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH27 riccardin C)

33 Cytotoxic Compounds

The bryophyte extracts apart from their antimicrobial activities showed cytotoxicactivities in vitro [387] The same was corroborated for some particular compounds Someof them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Agronomy 2022 12 1456 12 of 21

PC3 These compounds were tested on several human and mouse tumor lines breast cancerMCF-7 cellosaurus P388 chemoresistant prostate cancer PC3 glioblastoma multiforme U-251 leukemia HL-60 liver cancer HepG2 melanoma RPMI-7951 and monocytic leukemiaU937 (Table 6 Figure 4)

Table 6 Cytotoxic compounds isolated from bryophytes with modern uses

Compounds Species Family Activity Against Ref

Jungermannenone A(28 R=OH)

Jungermannenone B(29 R=H)

Jungermannia species L Jungermanniaceae

Human leukemia HL-60 cells(JA IC50

1 13 microM)PC3 (JA 15 micromolL JB

5 micromolL)

[399]

Lunularin (6) Dumortiera hirsuta (Sw)Nees Weisnerellaceae HepG2 (IC50 = 74 microgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Human MCF-7 breastcancer (IC50 40 microgmL)

chemoresistant prostate cancerPC3 cells

A375 melanoma cells(IC50 = 745ndash1197 microgmL)

[3100101]

Marsupellone (30) Marsupella emarginata(Ehrh) Dumort Gymnomitriaceaea P388 cancer cell line

(ID50 1 microgmL) [88]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorpha LSchistochila glaucescens

(Hook) AEvans

MarchantiaceaeSchistochilaceae P388 cell line (IC50 8ndash18 microgmL) [102]

Pallidisetin A (31)Pallidisetin B (32)

Polytrichum pallidisetumFunck Polytrichaceae

Melanoma (RPMI-7951)Glioblastoma multiforme

(U-251)[103]

Plagiochin E (33) Plagiochasm intermediumLindenb amp Gottsche Aytoniaceae Chemoresistant prostate cancer

PC3 cells (IC50 599 micromolL) [100]

Riccardin C (27)

Plagiochasma intermediumLindenb amp Gottsche

Reboulia hemisphaerica (L)Raddi

Aytoniaceae Chemoresistant prostate cancerPC3 cells (IC50 322 micromolL) [100104]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae BSC cells [90]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae

Human melanoma(IC50 2ndash4 micromolL) Lu1

(IC50 57 micromolL)KB (IC50 32 micromolL)

LNCaP and ZR-75-1 cells(IC50 76 micromolL)

[105]

Trewiasine (34)

Isothecium subdiversiformeBroth

Thamnobryum sandeiBesch

BrachytheciaceaeNeckeraceae

U937 cells ascitic tumors S180hepatoma U14 solid tumor

Lewis lung carcinoma[106]

1 IC50 the concentration of a drug that is required for 50 inhibition of cell growth in vitro Bold numbersrefer to the chemical structures o Bold numbers refer to the chemical structures of compounds are presented inFigures 3 and 4

Agronomy 2022 12 1456 13 of 21Agronomy 2022 12 x FOR PEER REVIEW 13 of 21

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenone B R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds In several species of the Radula Dumort genus cannabinoid compounds have been

discovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated from Radula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor) Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests on mouse brains showed that this compound is bioavailable and selectively binds to CB1 and CB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to Δ9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenoneB R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds

In several species of the Radula Dumort genus cannabinoid compounds have beendiscovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated fromRadula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor)Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests onmouse brains showed that this compound is bioavailable and selectively binds to CB1 andCB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to ∆9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

References1 Cole TCH Hilger HH Goffinet B Bryophyte Phylogeny Poster (BPP) PeerJ Prepr 2019 7 e27571v3 [CrossRef]2 de Sousa F Foster PG Donoghue PCJ Schneider H Cox CJ Nuclear Protein Phylogenies Support the Monophyly of the

Three Bryophyte Groups (Bryophyta Schimp) New Phytol 2019 222 565ndash575 [CrossRef]

Agronomy 2022 12 1456 16 of 21

3 Asakawa Y Ludwiczuk A Nagashima F Chemical Constituents of Bryophytes Bio-and Chemical Diversity Biological Activityand Chemosystematics In Progress in the Chemistry of Organic Natural Products Springer Vienna Austria 2013 Volume 95pp 1ndash796 ISBN 9783709110843

4 Tuba Z Slack NG Stark LR (Eds) Bryophyte Ecology and Climate Change Cambridge University Press Cambridge UK 2011ISBN 978-0-521-75777-5

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High Species Diversity Low Endemism and Low Similarity Biodivers Conserv 2020 29 2663ndash2688 [CrossRef]7 Cannone N Convey P Guglielmin M Diversity Trends of Bryophytes in Continental Antarctica Polar Biol 2013 36 259ndash271

[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

Change In Photosynthesis in Bryophytes and Early Land Plants Hanson DT Rice SK Eds Springer Dordrecht The Netherlands2014 pp 309ndash324 ISBN 978-94-007-6988-5

9 Smith RJ Stark LR Habitat vs Dispersal Constraints on Bryophyte Diversity in the Mojave Desert USA J Arid Environ 2014102 76ndash81 [CrossRef]

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ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

39 587ndash596 [CrossRef]14 Ren H Wang F Ye W Zhang Q Han T Huang Y Chu G Hui D Guo Q Bryophyte Diversity Is Related to Vascular

Plant Diversity and Microhabitat under Disturbance in Karst Caves Ecol Indic 2021 120 106947 [CrossRef]15 Von Reuszlig SH Koumlnig WA Olefinic Isothiocyanates and Iminodithiocarbonates from the Liverwort Corsinia coriandrina Eur J

Org Chem 2005 2005 1184ndash1188 [CrossRef]16 Chandra S Chandra D Barh A Pankaj Pandey RK Sharma IP Bryophytes Hoard of Remedies an Ethno-Medicinal

Review J Tradit Complement Med 2016 7 94ndash98 [CrossRef] [PubMed]17 Krishnan VGM Pradeep DP Aswathy JM Krishnan R Lubaina AS Murugan K Wonder Herbals-Bryophytes of

the Ponmudi Hills of Southern Western Ghats Window Into the Need for Conservation World J Pharm Pharm Sci 2014 31548ndash1562

18 Glime J Medical Uses Medical Conditions In Bryophyte Ecology Michigan Technological University Houghton MI USA 2017p 5 Available online httpsdigitalcommonsmtueduoabooks4 (accessed on 6 October 2021)

19 Asakawa Y Biologically Active Compounds from Bryophytes Pure Appl Chem 2007 79 557ndash580 [CrossRef]20 Xie CF Lou HX Secondary Metabolites in Bryophytes An Ecological Aspect Chem Biodivers 2009 6 303ndash312 [CrossRef]21 Asakawa Y Ludwiczuk A Novakovic M Bukvicki D Anchang KY Bis-Bibenzyls Bibenzyls and Terpenoids in 33 Genera

of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

Austria 1982 pp 1ndash28523 Sabovljevic MS Sabovljevic AD Ikram NKK Peramuna A Bae H Simonsen HT BryophytesmdashAn Emerging Source for

Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

110649 [CrossRef]27 Zhu MZ Li Y Zhou JC Lu JH Zhu RX Qiao YN Zhang JZ Zong Y Wang X Jin XY et al Terpenoids from

the Chinese Liverwort Odontoschisma Grosseverrucosum and Their Antifungal Virulence Activity Phytochemistry 2020 174[CrossRef]

28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

41ndash49 [CrossRef]

Agronomy 2022 12 1456 17 of 21

35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

37 Valarezo E Tandazo O Galaacuten K Rosales J Beniacutetez Aacute Volatile Metabolites in Liverworts of Ecuador Metabolites 2020 10 92[CrossRef]

38 Saritas Y Sonwa MM Iznaguen H Koumlnig WA Muhle H Mues R Volatile Constituents in Mosses (Musci) Phytochemistry2001 57 443ndash457 [CrossRef]

39 Tosun G Yaylı B Oumlzdemir T Batan N Bozdeveci A Yaylı N Volatiles and Antimicrobial Activity of the Essential Oils ofthe Mosses Pseudoscleropodium purum Eurhynchium striatum and Eurhynchium angustirete Grown in Turkey Rec Nat Prod 2015 9237ndash242

40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

43 Sakurai K Tomiyama K Kawakami Y Yaguchi Y Asakawa Y Characteristic Scent from the Tahitian Liverwort CyathodiumFoetidissimum J Oleo Sci 2018 67 1265ndash1269 [CrossRef]

44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

45 Asakawa Y Joulain D Chemical Constituents of Unidentified Malaysian Liverwort Astrella () Species J Hattori Bot Lab 1995188 183ndash188 [CrossRef]

46 Toyota M Saito T Matsunami J Asakawa Y A Comparative Study on Three Chemo-Types of the Liverwort ConocephalumConicum Using Volatile Constituents Phytochemistry 1997 44 1265ndash1270 [CrossRef]

47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

48 Ludwiczuk A Komala I Pham A Bianchini JP Raharivelomanana P Asakawa Y Volatile Components from SelectedTahitian Liverworts Nat Prod Commun 2009 4 1387ndash1392 [CrossRef]

49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

51 Pannequin A Tintaru A Desjobert JM Costa J Muselli A New Advances in the Volatile Metabolites of Frullania tamarisciFlavour Fragr J 2017 32 409ndash418 [CrossRef]

52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

64 Vats S Alam A Antibacterial Activity of Atrichum undulatum (Hedw) P Beauv against Some Pathogenic Bacteria J Biol Sci2013 13 427ndash431 [CrossRef]

65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

68 Karpinski TM Adamczak A Antibacterial Activity of Ethanolic Extracts of Some Moss Species Herba Pol 2017 63 11ndash17[CrossRef]

69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

77 Nikolajeva V Liepina L Petrina Z Krumina G Grube M Muiznieks I Antibacterial Activity of Extracts from SomeBryophytes Adv Microbiol 2012 02 345ndash353 [CrossRef]

78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

79 Basile A Giordano S Sorbo S Vuotto ML Ielpo MTL Cobianchi RC Antibiotic Effects of Lunularia cruciata (Bryophyta)Extract Pharm Biol 1998 36 25ndash28 [CrossRef]

80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 6: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 6 of 21

tivities of their extracts against selected pathogens Gram-negative bacteria show greatersensitivity to extracts obtained from bryophytes This makes them potential complementsfor antibiotics as conventional antibiotics tend to be more active against Gram-positivebacteria [1861] This phenomenon is rare in higher plants [62] The metabolites showingantibacterial activity isolated from the extracts are unique to bryophytes Among themlunularin (21) marchantin A (29) polygodial (30) riccardiphenol C (32) and sacculatal wereisolated (Table 4 Figure 2) They show activity against ie Acinetobacter calcoaceticusBacillus cereus B subtilis Cryptococcus neoformans Pseudomonas aeruginosa Salmonellatyphimurium Staphylococcus aureus and Streptococcus mutans

Table 3 Antimicrobial activities of some bryophyte extracts

Division Species Extracts Tested Bacteria Tested Fungi Ref

Bryo

phyt

a

Atrichumundulatum

(Hedw) PBeauv

Waterethanol

Bacillus mycoidesEscherichia coli

Proteus mirabilisStaphylococcus aureus

Salmonella typhii

Aspergillus fumigatusFusarium oxysporum [6364]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Bryumargenteum

HedwEthanol

Escherichia coliBacillus subtilis

Micrococcus luteusStaphilococcus aureus

Aspergillus nigerPenicillium ochrochloron

Candida albicansTrichophyton mentagrophyes

[67]

Dicranum scopariumHedw Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureusStreptococcus pyogenes

NT [68]

Fontinalis antipyreticaHedw Methanol

Escherichia coliSalmonella enteritidisShigella epidermidis

Bacillus subtilisMicrococcus flavus

Aspergillus flavusA fumigatus

A nigerPenicillium funiculosum

P ochrochloronTrichoderma viride

[69]

Hypnum cupressiformeHedw

Methanol

Bacillus subtilisEscherichia coli

Micrococcus flavusShigella enteritidis

S epidermidis

Aspergillus flavusA fumigatus

A nigerPenicillium funiculosum

P ochrochloronTrichoderma viride

[69]

Water NS Candida albicansSaccharomyces cerevisiae [70]

Plagiomniumcuspidatum

(Hedw) TJKopn-hexane

Bacillus subtilisMoraxella catarrhalis

Staphylococcus aureusShigella epidermidis

Streptococcus pyogenesS pneumonianiae

NT [71]

Agronomy 2022 12 1456 7 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Polytrichum communeHedw

Water

Escherichia coliEnterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NT [72]

Chloroformethanol

Bacillus cereusEscherichia coli

Enterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NS [73]

Polytrichumjuniperinum

Hedw

MethanolBacillus subtilis

Pseudomonas aeruginosaStaphylococcus aureus

NT [74]

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Syntrichiaruralis

(Hedw) F Weber amp DMohr

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Mar

chan

tioph

yta

Bazzania trilobata L

Dichloromethanemethanol NT

Botrytis cinereaCandida albicans

Cladosporium cucumerinumPhythophthora infestans

Pyricularia oryzaeSeptoria tritici

[75]

EthanolBacillus subtilis

Listeria monocytogenesStaphylococcus aureus

NS [76]

Frullaniadilatata

(L) Dumort

Waterethanol Staphylococcus aureus NT [77]

Lophozia ventricosa(Dicks) Dumort

Methanolethyl acetate

Bacillus cereusListeria monocytogenes

Micrococcus flavusStaphylococcus aureus

Aspergillus nigerA fumigatesA ochraceusA versicolor

Penicillium funiculosumP ochrochloron

Trichoderma viride

[78]

Agronomy 2022 12 1456 8 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Lunulariacruciata

(L) Lindb

Acetonechloroform

ethanolmethanol

water

Agrobacterium tumefaciensStaphylococcus aureusShigella epidermidis

Streptococcus faecalisProteus mirabilis

P vulgarisPseudomonas aeruginosa

Escherichia coliSalmonella typhi

Klebsiella pneumoniaeEnterobacter cloacae

E aerogenesCitrobacter diversus

Bacillus subtilisXanthomonas phoseoliErwinia chrysanthemi

NS [7980]

Marchantia polymorphaL

Chloroformmethanol

Escherichia coliStaphylococcus aureus

Proteus mirabilisPasturella multocidaXanthomonas oryzae

Candida albicansFusarium oxysporum

Rhizoctonia solaniSclerotium rolfsii

Trichophyton mentagrohtytesTilletia indica

[8182]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Porellaarboris-vitae

(With) Grolle

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

Pichia anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[83]

RebouliaHemisphaerica(L)

RaddiMethanol

Bacillus cereus B subtilisEscherichia coli

Enterococcus faecalisPseudomonas aeruginosa

Staphylococcus aureus

Aspergillus nigerPenicillium notatum [84]

Scapania asperaM Bernet amp Bernet

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

P anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[61]

Targioniahypophylla L Methanol

Bacillus substilisEscherichia coli

Staphylococcus aureus

Aspergillus nigerBotrytis cinerea

Penicillium chrysogenumP expansum

Trichoderma viridae

[8586]

Distillation NTmdashnot tested NSmdashnot shown

Agronomy 2022 12 1456 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)Nees Dumortieraceae Pseudomonas aeruginosa (MIC

64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC125 microgmL)

Bacillus cereus (125 microgmL)Bacillus megaterium (MIC

25 microgmL)Bacillus subtilis (MIC25 microgmL)

Cryptococcus neoformans (MIC125 microgmL) Staphylococcus aureus

(MIC 313ndash25)Salmonella typhimurium (MIC

100 microgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50100 microgmL) [19]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae Streptococcus mutans (LD50

8 microgmL) [19]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdashminimuminhibitory concentration Bold numbers refer to the chemical structures o Bold numbers refer to the chemicalstructures of compounds are presented in Figures 1 and 2

Agronomy 2022 12 x FOR PEER REVIEW 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)

Nees Dumortieraceae Pseudomonas aeruginosa (MIC 64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC 125 μgmL)

Bacillus cereus (125 μgmL)

Bacillus megaterium (MIC 25 μgmL)

Bacillus subtilis (MIC25 μgmL)

Cryptococcus neoformans (MIC 125 μgmL)

Staphylococcus aureus (MIC 313ndash25)

Salmonella typhimurium (MIC 100 μgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50 100 μgmL) [19]

Sacculatal (15) Pellia endiviifolia (Dicks)

Dumort Pelliaceae Streptococcus mutans (LD50 8 μgmL) [19]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdash

minimum inhibitory concentration Bold numbers refer to the chemical structures o Bold numbers

refer to the chemical structures of compounds are presented in Figures 1 and 2

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygo-

dial 15 sacculatal 16 riccardiphenol C)

Apart from their antibacterial potential bryophyte extracts show antifungal proper-

ties The results of the research show that the extracts of certain species of mosses and

liverworts do not exhibit these properties despite their antibacterial effects [737980]

Such selectivity may have industrial or medical applications [4791ndash93] On the other

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygodial15 sacculatal 16 riccardiphenol C)

Agronomy 2022 12 1456 10 of 21

Apart from their antibacterial potential bryophyte extracts show antifungal proper-ties The results of the research show that the extracts of certain species of mosses andliverworts do not exhibit these properties despite their antibacterial effects [737980] Suchselectivity may have industrial or medical applications [4791ndash93] On the other hand theisolated antifungal substances show activity against numerous pathogenic fungi (Table 5Figure 3) [7588ndash9094ndash97]

Table 5 Antifungal activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Asterelin A (17 R=H)Asterelin B (18 R=Me)

Asterella angusta(Stephani) Pandeacute KPSrivast amp Sultan Khan

Aytoniaceae Candida albicans [94]

Bazzanin B (19 R=Cl)Bazzanin S (20 R=H) Bazzania trilobata L Lepidoziaceae

Botrytis cinerea (IC50 189)Cladosporium cucumerinum (IC50

175)Pyricularia oryzae (IC50 39)

Zymoseptoria tritici (IC50 235)

[75]

Isoplagiochin D (21)Bazzania trilobata LLepidozia incurvata

LindenbLepidoziaceae Zymoseptoria tritici (IC50 159) [95]

Isoriccardin C (22)Plagiochasmaintermedium

Lindenb amp GottscheAytoniaceae Candida albicans [95]

Gymnomitrol (23)Bazzania trilobata L

Gymnomitrion obtusum(Lindb) Pears

LepidoziaceaeGymnomitriaceae

Phytophthora infestansPyricularia oryzae

Zymoseptoria tritici[7598]

Marchantin A (13) Marchantia species L Marchantiaceae

Aspergillus niger (MIC25-100 microgmL)

Pyricularia oryzae (MIC125 microgmL)

Rhizoctonia solani (MIC 50 microgmL)Saccharomyces cerevisiae (MIC

313 microgmL)Trichophyton mentagrophytes (MIC

313 microgmL)

[8889]

Marchantin H (24)

Marchantia polymorphaL

Plagiochasmaintermedium Lindenb amp

Gotische

MarchantiaceaAytoniaceae Candida albicans (MIC 256 microgmL) [97]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorphaL Marchantiaceae Candida albicans [96]

Riccardin C (27)

Asterella angusta(Stephani) Pandeacute KP

Sri-vast amp Sultan KhanPlagiochasma

intermedium Lindenb ampGotische

AytoniaceaeAytoniaceae Candida albicans [97]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Candida albicans

Trichophyton mtagropbytes [90]

IC50 the concentration of a drug that is required for 50 inhibition in vitro MICmdashminimum inhibitory concentra-tion Bold numbers refer to the chemical structures o Bold numbers refer to the chemical structures of compoundsare presented in Figures 2 and 3

Agronomy 2022 12 1456 11 of 21Agronomy 2022 12 x FOR PEER REVIEW 11 of 21

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 asterelin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardin C 23 gym-nomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH 27 riccardin C)

33 Cytotoxic Compounds The bryophyte extracts apart from their antimicrobial activities showed cytotoxic

activities in vitro [387] The same was corroborated for some particular compounds Some of them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 aster-elin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardinC 23 gymnomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH27 riccardin C)

33 Cytotoxic Compounds

The bryophyte extracts apart from their antimicrobial activities showed cytotoxicactivities in vitro [387] The same was corroborated for some particular compounds Someof them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Agronomy 2022 12 1456 12 of 21

PC3 These compounds were tested on several human and mouse tumor lines breast cancerMCF-7 cellosaurus P388 chemoresistant prostate cancer PC3 glioblastoma multiforme U-251 leukemia HL-60 liver cancer HepG2 melanoma RPMI-7951 and monocytic leukemiaU937 (Table 6 Figure 4)

Table 6 Cytotoxic compounds isolated from bryophytes with modern uses

Compounds Species Family Activity Against Ref

Jungermannenone A(28 R=OH)

Jungermannenone B(29 R=H)

Jungermannia species L Jungermanniaceae

Human leukemia HL-60 cells(JA IC50

1 13 microM)PC3 (JA 15 micromolL JB

5 micromolL)

[399]

Lunularin (6) Dumortiera hirsuta (Sw)Nees Weisnerellaceae HepG2 (IC50 = 74 microgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Human MCF-7 breastcancer (IC50 40 microgmL)

chemoresistant prostate cancerPC3 cells

A375 melanoma cells(IC50 = 745ndash1197 microgmL)

[3100101]

Marsupellone (30) Marsupella emarginata(Ehrh) Dumort Gymnomitriaceaea P388 cancer cell line

(ID50 1 microgmL) [88]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorpha LSchistochila glaucescens

(Hook) AEvans

MarchantiaceaeSchistochilaceae P388 cell line (IC50 8ndash18 microgmL) [102]

Pallidisetin A (31)Pallidisetin B (32)

Polytrichum pallidisetumFunck Polytrichaceae

Melanoma (RPMI-7951)Glioblastoma multiforme

(U-251)[103]

Plagiochin E (33) Plagiochasm intermediumLindenb amp Gottsche Aytoniaceae Chemoresistant prostate cancer

PC3 cells (IC50 599 micromolL) [100]

Riccardin C (27)

Plagiochasma intermediumLindenb amp Gottsche

Reboulia hemisphaerica (L)Raddi

Aytoniaceae Chemoresistant prostate cancerPC3 cells (IC50 322 micromolL) [100104]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae BSC cells [90]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae

Human melanoma(IC50 2ndash4 micromolL) Lu1

(IC50 57 micromolL)KB (IC50 32 micromolL)

LNCaP and ZR-75-1 cells(IC50 76 micromolL)

[105]

Trewiasine (34)

Isothecium subdiversiformeBroth

Thamnobryum sandeiBesch

BrachytheciaceaeNeckeraceae

U937 cells ascitic tumors S180hepatoma U14 solid tumor

Lewis lung carcinoma[106]

1 IC50 the concentration of a drug that is required for 50 inhibition of cell growth in vitro Bold numbersrefer to the chemical structures o Bold numbers refer to the chemical structures of compounds are presented inFigures 3 and 4

Agronomy 2022 12 1456 13 of 21Agronomy 2022 12 x FOR PEER REVIEW 13 of 21

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenone B R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds In several species of the Radula Dumort genus cannabinoid compounds have been

discovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated from Radula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor) Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests on mouse brains showed that this compound is bioavailable and selectively binds to CB1 and CB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to Δ9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenoneB R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds

In several species of the Radula Dumort genus cannabinoid compounds have beendiscovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated fromRadula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor)Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests onmouse brains showed that this compound is bioavailable and selectively binds to CB1 andCB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to ∆9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

References1 Cole TCH Hilger HH Goffinet B Bryophyte Phylogeny Poster (BPP) PeerJ Prepr 2019 7 e27571v3 [CrossRef]2 de Sousa F Foster PG Donoghue PCJ Schneider H Cox CJ Nuclear Protein Phylogenies Support the Monophyly of the

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Agronomy 2022 12 1456 16 of 21

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[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

Change In Photosynthesis in Bryophytes and Early Land Plants Hanson DT Rice SK Eds Springer Dordrecht The Netherlands2014 pp 309ndash324 ISBN 978-94-007-6988-5

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ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

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Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

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28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

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Agronomy 2022 12 1456 17 of 21

35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

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40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

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44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

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47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

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49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

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52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

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62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

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66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

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70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

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73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

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75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

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80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

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103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 7: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 7 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Polytrichum communeHedw

Water

Escherichia coliEnterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NT [72]

Chloroformethanol

Bacillus cereusEscherichia coli

Enterococcus faecalisStreptococcus mutans

Pseudomonas aeruginosaStaphylococcus aureus

NS [73]

Polytrichumjuniperinum

Hedw

MethanolBacillus subtilis

Pseudomonas aeruginosaStaphylococcus aureus

NT [74]

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Syntrichiaruralis

(Hedw) F Weber amp DMohr

Ethanol

Enterococcus faecalisEscherichia coli

Klebsiella pneumoniaStaphylococcus aureus

NT [68]

Mar

chan

tioph

yta

Bazzania trilobata L

Dichloromethanemethanol NT

Botrytis cinereaCandida albicans

Cladosporium cucumerinumPhythophthora infestans

Pyricularia oryzaeSeptoria tritici

[75]

EthanolBacillus subtilis

Listeria monocytogenesStaphylococcus aureus

NS [76]

Frullaniadilatata

(L) Dumort

Waterethanol Staphylococcus aureus NT [77]

Lophozia ventricosa(Dicks) Dumort

Methanolethyl acetate

Bacillus cereusListeria monocytogenes

Micrococcus flavusStaphylococcus aureus

Aspergillus nigerA fumigatesA ochraceusA versicolor

Penicillium funiculosumP ochrochloron

Trichoderma viride

[78]

Agronomy 2022 12 1456 8 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Lunulariacruciata

(L) Lindb

Acetonechloroform

ethanolmethanol

water

Agrobacterium tumefaciensStaphylococcus aureusShigella epidermidis

Streptococcus faecalisProteus mirabilis

P vulgarisPseudomonas aeruginosa

Escherichia coliSalmonella typhi

Klebsiella pneumoniaeEnterobacter cloacae

E aerogenesCitrobacter diversus

Bacillus subtilisXanthomonas phoseoliErwinia chrysanthemi

NS [7980]

Marchantia polymorphaL

Chloroformmethanol

Escherichia coliStaphylococcus aureus

Proteus mirabilisPasturella multocidaXanthomonas oryzae

Candida albicansFusarium oxysporum

Rhizoctonia solaniSclerotium rolfsii

Trichophyton mentagrohtytesTilletia indica

[8182]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Porellaarboris-vitae

(With) Grolle

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

Pichia anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[83]

RebouliaHemisphaerica(L)

RaddiMethanol

Bacillus cereus B subtilisEscherichia coli

Enterococcus faecalisPseudomonas aeruginosa

Staphylococcus aureus

Aspergillus nigerPenicillium notatum [84]

Scapania asperaM Bernet amp Bernet

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

P anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[61]

Targioniahypophylla L Methanol

Bacillus substilisEscherichia coli

Staphylococcus aureus

Aspergillus nigerBotrytis cinerea

Penicillium chrysogenumP expansum

Trichoderma viridae

[8586]

Distillation NTmdashnot tested NSmdashnot shown

Agronomy 2022 12 1456 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)Nees Dumortieraceae Pseudomonas aeruginosa (MIC

64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC125 microgmL)

Bacillus cereus (125 microgmL)Bacillus megaterium (MIC

25 microgmL)Bacillus subtilis (MIC25 microgmL)

Cryptococcus neoformans (MIC125 microgmL) Staphylococcus aureus

(MIC 313ndash25)Salmonella typhimurium (MIC

100 microgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50100 microgmL) [19]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae Streptococcus mutans (LD50

8 microgmL) [19]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdashminimuminhibitory concentration Bold numbers refer to the chemical structures o Bold numbers refer to the chemicalstructures of compounds are presented in Figures 1 and 2

Agronomy 2022 12 x FOR PEER REVIEW 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)

Nees Dumortieraceae Pseudomonas aeruginosa (MIC 64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC 125 μgmL)

Bacillus cereus (125 μgmL)

Bacillus megaterium (MIC 25 μgmL)

Bacillus subtilis (MIC25 μgmL)

Cryptococcus neoformans (MIC 125 μgmL)

Staphylococcus aureus (MIC 313ndash25)

Salmonella typhimurium (MIC 100 μgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50 100 μgmL) [19]

Sacculatal (15) Pellia endiviifolia (Dicks)

Dumort Pelliaceae Streptococcus mutans (LD50 8 μgmL) [19]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdash

minimum inhibitory concentration Bold numbers refer to the chemical structures o Bold numbers

refer to the chemical structures of compounds are presented in Figures 1 and 2

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygo-

dial 15 sacculatal 16 riccardiphenol C)

Apart from their antibacterial potential bryophyte extracts show antifungal proper-

ties The results of the research show that the extracts of certain species of mosses and

liverworts do not exhibit these properties despite their antibacterial effects [737980]

Such selectivity may have industrial or medical applications [4791ndash93] On the other

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygodial15 sacculatal 16 riccardiphenol C)

Agronomy 2022 12 1456 10 of 21

Apart from their antibacterial potential bryophyte extracts show antifungal proper-ties The results of the research show that the extracts of certain species of mosses andliverworts do not exhibit these properties despite their antibacterial effects [737980] Suchselectivity may have industrial or medical applications [4791ndash93] On the other hand theisolated antifungal substances show activity against numerous pathogenic fungi (Table 5Figure 3) [7588ndash9094ndash97]

Table 5 Antifungal activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Asterelin A (17 R=H)Asterelin B (18 R=Me)

Asterella angusta(Stephani) Pandeacute KPSrivast amp Sultan Khan

Aytoniaceae Candida albicans [94]

Bazzanin B (19 R=Cl)Bazzanin S (20 R=H) Bazzania trilobata L Lepidoziaceae

Botrytis cinerea (IC50 189)Cladosporium cucumerinum (IC50

175)Pyricularia oryzae (IC50 39)

Zymoseptoria tritici (IC50 235)

[75]

Isoplagiochin D (21)Bazzania trilobata LLepidozia incurvata

LindenbLepidoziaceae Zymoseptoria tritici (IC50 159) [95]

Isoriccardin C (22)Plagiochasmaintermedium

Lindenb amp GottscheAytoniaceae Candida albicans [95]

Gymnomitrol (23)Bazzania trilobata L

Gymnomitrion obtusum(Lindb) Pears

LepidoziaceaeGymnomitriaceae

Phytophthora infestansPyricularia oryzae

Zymoseptoria tritici[7598]

Marchantin A (13) Marchantia species L Marchantiaceae

Aspergillus niger (MIC25-100 microgmL)

Pyricularia oryzae (MIC125 microgmL)

Rhizoctonia solani (MIC 50 microgmL)Saccharomyces cerevisiae (MIC

313 microgmL)Trichophyton mentagrophytes (MIC

313 microgmL)

[8889]

Marchantin H (24)

Marchantia polymorphaL

Plagiochasmaintermedium Lindenb amp

Gotische

MarchantiaceaAytoniaceae Candida albicans (MIC 256 microgmL) [97]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorphaL Marchantiaceae Candida albicans [96]

Riccardin C (27)

Asterella angusta(Stephani) Pandeacute KP

Sri-vast amp Sultan KhanPlagiochasma

intermedium Lindenb ampGotische

AytoniaceaeAytoniaceae Candida albicans [97]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Candida albicans

Trichophyton mtagropbytes [90]

IC50 the concentration of a drug that is required for 50 inhibition in vitro MICmdashminimum inhibitory concentra-tion Bold numbers refer to the chemical structures o Bold numbers refer to the chemical structures of compoundsare presented in Figures 2 and 3

Agronomy 2022 12 1456 11 of 21Agronomy 2022 12 x FOR PEER REVIEW 11 of 21

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 asterelin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardin C 23 gym-nomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH 27 riccardin C)

33 Cytotoxic Compounds The bryophyte extracts apart from their antimicrobial activities showed cytotoxic

activities in vitro [387] The same was corroborated for some particular compounds Some of them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 aster-elin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardinC 23 gymnomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH27 riccardin C)

33 Cytotoxic Compounds

The bryophyte extracts apart from their antimicrobial activities showed cytotoxicactivities in vitro [387] The same was corroborated for some particular compounds Someof them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Agronomy 2022 12 1456 12 of 21

PC3 These compounds were tested on several human and mouse tumor lines breast cancerMCF-7 cellosaurus P388 chemoresistant prostate cancer PC3 glioblastoma multiforme U-251 leukemia HL-60 liver cancer HepG2 melanoma RPMI-7951 and monocytic leukemiaU937 (Table 6 Figure 4)

Table 6 Cytotoxic compounds isolated from bryophytes with modern uses

Compounds Species Family Activity Against Ref

Jungermannenone A(28 R=OH)

Jungermannenone B(29 R=H)

Jungermannia species L Jungermanniaceae

Human leukemia HL-60 cells(JA IC50

1 13 microM)PC3 (JA 15 micromolL JB

5 micromolL)

[399]

Lunularin (6) Dumortiera hirsuta (Sw)Nees Weisnerellaceae HepG2 (IC50 = 74 microgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Human MCF-7 breastcancer (IC50 40 microgmL)

chemoresistant prostate cancerPC3 cells

A375 melanoma cells(IC50 = 745ndash1197 microgmL)

[3100101]

Marsupellone (30) Marsupella emarginata(Ehrh) Dumort Gymnomitriaceaea P388 cancer cell line

(ID50 1 microgmL) [88]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorpha LSchistochila glaucescens

(Hook) AEvans

MarchantiaceaeSchistochilaceae P388 cell line (IC50 8ndash18 microgmL) [102]

Pallidisetin A (31)Pallidisetin B (32)

Polytrichum pallidisetumFunck Polytrichaceae

Melanoma (RPMI-7951)Glioblastoma multiforme

(U-251)[103]

Plagiochin E (33) Plagiochasm intermediumLindenb amp Gottsche Aytoniaceae Chemoresistant prostate cancer

PC3 cells (IC50 599 micromolL) [100]

Riccardin C (27)

Plagiochasma intermediumLindenb amp Gottsche

Reboulia hemisphaerica (L)Raddi

Aytoniaceae Chemoresistant prostate cancerPC3 cells (IC50 322 micromolL) [100104]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae BSC cells [90]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae

Human melanoma(IC50 2ndash4 micromolL) Lu1

(IC50 57 micromolL)KB (IC50 32 micromolL)

LNCaP and ZR-75-1 cells(IC50 76 micromolL)

[105]

Trewiasine (34)

Isothecium subdiversiformeBroth

Thamnobryum sandeiBesch

BrachytheciaceaeNeckeraceae

U937 cells ascitic tumors S180hepatoma U14 solid tumor

Lewis lung carcinoma[106]

1 IC50 the concentration of a drug that is required for 50 inhibition of cell growth in vitro Bold numbersrefer to the chemical structures o Bold numbers refer to the chemical structures of compounds are presented inFigures 3 and 4

Agronomy 2022 12 1456 13 of 21Agronomy 2022 12 x FOR PEER REVIEW 13 of 21

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenone B R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds In several species of the Radula Dumort genus cannabinoid compounds have been

discovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated from Radula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor) Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests on mouse brains showed that this compound is bioavailable and selectively binds to CB1 and CB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to Δ9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenoneB R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds

In several species of the Radula Dumort genus cannabinoid compounds have beendiscovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated fromRadula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor)Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests onmouse brains showed that this compound is bioavailable and selectively binds to CB1 andCB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to ∆9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

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Agronomy 2022 12 1456 16 of 21

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35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

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40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

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Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

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66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

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81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

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86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

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Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

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99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

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103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

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107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

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110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

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112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

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Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

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121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

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132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 8: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 8 of 21

Table 3 Cont

Division Species Extracts Tested Bacteria Tested Fungi Ref

Lunulariacruciata

(L) Lindb

Acetonechloroform

ethanolmethanol

water

Agrobacterium tumefaciensStaphylococcus aureusShigella epidermidis

Streptococcus faecalisProteus mirabilis

P vulgarisPseudomonas aeruginosa

Escherichia coliSalmonella typhi

Klebsiella pneumoniaeEnterobacter cloacae

E aerogenesCitrobacter diversus

Bacillus subtilisXanthomonas phoseoliErwinia chrysanthemi

NS [7980]

Marchantia polymorphaL

Chloroformmethanol

Escherichia coliStaphylococcus aureus

Proteus mirabilisPasturella multocidaXanthomonas oryzae

Candida albicansFusarium oxysporum

Rhizoctonia solaniSclerotium rolfsii

Trichophyton mentagrohtytesTilletia indica

[8182]

Dimethylsulfoxyde

Bacillus cereusEscherichia coli

Micrococcus flavusStaphylococcus aureus

Aspergillus fumigatusPenicillium funiculosum

P ochrocholoronTrichoderma viride

[6566]

Porellaarboris-vitae

(With) Grolle

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

Pichia anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[83]

RebouliaHemisphaerica(L)

RaddiMethanol

Bacillus cereus B subtilisEscherichia coli

Enterococcus faecalisPseudomonas aeruginosa

Staphylococcus aureus

Aspergillus nigerPenicillium notatum [84]

Scapania asperaM Bernet amp Bernet

Methanolethanol ethyl

acetate

Salmonella enteritidisEscherichia coli

Listeria monocytogenes

Aerobasidium pullulansPichia membranaefaciens

P anomalaSaccharomyces cerevisiaeZygosaccharomyces bailii

[61]

Targioniahypophylla L Methanol

Bacillus substilisEscherichia coli

Staphylococcus aureus

Aspergillus nigerBotrytis cinerea

Penicillium chrysogenumP expansum

Trichoderma viridae

[8586]

Distillation NTmdashnot tested NSmdashnot shown

Agronomy 2022 12 1456 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)Nees Dumortieraceae Pseudomonas aeruginosa (MIC

64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC125 microgmL)

Bacillus cereus (125 microgmL)Bacillus megaterium (MIC

25 microgmL)Bacillus subtilis (MIC25 microgmL)

Cryptococcus neoformans (MIC125 microgmL) Staphylococcus aureus

(MIC 313ndash25)Salmonella typhimurium (MIC

100 microgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50100 microgmL) [19]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae Streptococcus mutans (LD50

8 microgmL) [19]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdashminimuminhibitory concentration Bold numbers refer to the chemical structures o Bold numbers refer to the chemicalstructures of compounds are presented in Figures 1 and 2

Agronomy 2022 12 x FOR PEER REVIEW 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)

Nees Dumortieraceae Pseudomonas aeruginosa (MIC 64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC 125 μgmL)

Bacillus cereus (125 μgmL)

Bacillus megaterium (MIC 25 μgmL)

Bacillus subtilis (MIC25 μgmL)

Cryptococcus neoformans (MIC 125 μgmL)

Staphylococcus aureus (MIC 313ndash25)

Salmonella typhimurium (MIC 100 μgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50 100 μgmL) [19]

Sacculatal (15) Pellia endiviifolia (Dicks)

Dumort Pelliaceae Streptococcus mutans (LD50 8 μgmL) [19]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdash

minimum inhibitory concentration Bold numbers refer to the chemical structures o Bold numbers

refer to the chemical structures of compounds are presented in Figures 1 and 2

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygo-

dial 15 sacculatal 16 riccardiphenol C)

Apart from their antibacterial potential bryophyte extracts show antifungal proper-

ties The results of the research show that the extracts of certain species of mosses and

liverworts do not exhibit these properties despite their antibacterial effects [737980]

Such selectivity may have industrial or medical applications [4791ndash93] On the other

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygodial15 sacculatal 16 riccardiphenol C)

Agronomy 2022 12 1456 10 of 21

Apart from their antibacterial potential bryophyte extracts show antifungal proper-ties The results of the research show that the extracts of certain species of mosses andliverworts do not exhibit these properties despite their antibacterial effects [737980] Suchselectivity may have industrial or medical applications [4791ndash93] On the other hand theisolated antifungal substances show activity against numerous pathogenic fungi (Table 5Figure 3) [7588ndash9094ndash97]

Table 5 Antifungal activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Asterelin A (17 R=H)Asterelin B (18 R=Me)

Asterella angusta(Stephani) Pandeacute KPSrivast amp Sultan Khan

Aytoniaceae Candida albicans [94]

Bazzanin B (19 R=Cl)Bazzanin S (20 R=H) Bazzania trilobata L Lepidoziaceae

Botrytis cinerea (IC50 189)Cladosporium cucumerinum (IC50

175)Pyricularia oryzae (IC50 39)

Zymoseptoria tritici (IC50 235)

[75]

Isoplagiochin D (21)Bazzania trilobata LLepidozia incurvata

LindenbLepidoziaceae Zymoseptoria tritici (IC50 159) [95]

Isoriccardin C (22)Plagiochasmaintermedium

Lindenb amp GottscheAytoniaceae Candida albicans [95]

Gymnomitrol (23)Bazzania trilobata L

Gymnomitrion obtusum(Lindb) Pears

LepidoziaceaeGymnomitriaceae

Phytophthora infestansPyricularia oryzae

Zymoseptoria tritici[7598]

Marchantin A (13) Marchantia species L Marchantiaceae

Aspergillus niger (MIC25-100 microgmL)

Pyricularia oryzae (MIC125 microgmL)

Rhizoctonia solani (MIC 50 microgmL)Saccharomyces cerevisiae (MIC

313 microgmL)Trichophyton mentagrophytes (MIC

313 microgmL)

[8889]

Marchantin H (24)

Marchantia polymorphaL

Plagiochasmaintermedium Lindenb amp

Gotische

MarchantiaceaAytoniaceae Candida albicans (MIC 256 microgmL) [97]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorphaL Marchantiaceae Candida albicans [96]

Riccardin C (27)

Asterella angusta(Stephani) Pandeacute KP

Sri-vast amp Sultan KhanPlagiochasma

intermedium Lindenb ampGotische

AytoniaceaeAytoniaceae Candida albicans [97]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Candida albicans

Trichophyton mtagropbytes [90]

IC50 the concentration of a drug that is required for 50 inhibition in vitro MICmdashminimum inhibitory concentra-tion Bold numbers refer to the chemical structures o Bold numbers refer to the chemical structures of compoundsare presented in Figures 2 and 3

Agronomy 2022 12 1456 11 of 21Agronomy 2022 12 x FOR PEER REVIEW 11 of 21

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 asterelin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardin C 23 gym-nomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH 27 riccardin C)

33 Cytotoxic Compounds The bryophyte extracts apart from their antimicrobial activities showed cytotoxic

activities in vitro [387] The same was corroborated for some particular compounds Some of them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 aster-elin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardinC 23 gymnomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH27 riccardin C)

33 Cytotoxic Compounds

The bryophyte extracts apart from their antimicrobial activities showed cytotoxicactivities in vitro [387] The same was corroborated for some particular compounds Someof them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Agronomy 2022 12 1456 12 of 21

PC3 These compounds were tested on several human and mouse tumor lines breast cancerMCF-7 cellosaurus P388 chemoresistant prostate cancer PC3 glioblastoma multiforme U-251 leukemia HL-60 liver cancer HepG2 melanoma RPMI-7951 and monocytic leukemiaU937 (Table 6 Figure 4)

Table 6 Cytotoxic compounds isolated from bryophytes with modern uses

Compounds Species Family Activity Against Ref

Jungermannenone A(28 R=OH)

Jungermannenone B(29 R=H)

Jungermannia species L Jungermanniaceae

Human leukemia HL-60 cells(JA IC50

1 13 microM)PC3 (JA 15 micromolL JB

5 micromolL)

[399]

Lunularin (6) Dumortiera hirsuta (Sw)Nees Weisnerellaceae HepG2 (IC50 = 74 microgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Human MCF-7 breastcancer (IC50 40 microgmL)

chemoresistant prostate cancerPC3 cells

A375 melanoma cells(IC50 = 745ndash1197 microgmL)

[3100101]

Marsupellone (30) Marsupella emarginata(Ehrh) Dumort Gymnomitriaceaea P388 cancer cell line

(ID50 1 microgmL) [88]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorpha LSchistochila glaucescens

(Hook) AEvans

MarchantiaceaeSchistochilaceae P388 cell line (IC50 8ndash18 microgmL) [102]

Pallidisetin A (31)Pallidisetin B (32)

Polytrichum pallidisetumFunck Polytrichaceae

Melanoma (RPMI-7951)Glioblastoma multiforme

(U-251)[103]

Plagiochin E (33) Plagiochasm intermediumLindenb amp Gottsche Aytoniaceae Chemoresistant prostate cancer

PC3 cells (IC50 599 micromolL) [100]

Riccardin C (27)

Plagiochasma intermediumLindenb amp Gottsche

Reboulia hemisphaerica (L)Raddi

Aytoniaceae Chemoresistant prostate cancerPC3 cells (IC50 322 micromolL) [100104]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae BSC cells [90]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae

Human melanoma(IC50 2ndash4 micromolL) Lu1

(IC50 57 micromolL)KB (IC50 32 micromolL)

LNCaP and ZR-75-1 cells(IC50 76 micromolL)

[105]

Trewiasine (34)

Isothecium subdiversiformeBroth

Thamnobryum sandeiBesch

BrachytheciaceaeNeckeraceae

U937 cells ascitic tumors S180hepatoma U14 solid tumor

Lewis lung carcinoma[106]

1 IC50 the concentration of a drug that is required for 50 inhibition of cell growth in vitro Bold numbersrefer to the chemical structures o Bold numbers refer to the chemical structures of compounds are presented inFigures 3 and 4

Agronomy 2022 12 1456 13 of 21Agronomy 2022 12 x FOR PEER REVIEW 13 of 21

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenone B R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds In several species of the Radula Dumort genus cannabinoid compounds have been

discovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated from Radula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor) Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests on mouse brains showed that this compound is bioavailable and selectively binds to CB1 and CB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to Δ9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenoneB R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds

In several species of the Radula Dumort genus cannabinoid compounds have beendiscovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated fromRadula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor)Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests onmouse brains showed that this compound is bioavailable and selectively binds to CB1 andCB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to ∆9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

References1 Cole TCH Hilger HH Goffinet B Bryophyte Phylogeny Poster (BPP) PeerJ Prepr 2019 7 e27571v3 [CrossRef]2 de Sousa F Foster PG Donoghue PCJ Schneider H Cox CJ Nuclear Protein Phylogenies Support the Monophyly of the

Three Bryophyte Groups (Bryophyta Schimp) New Phytol 2019 222 565ndash575 [CrossRef]

Agronomy 2022 12 1456 16 of 21

3 Asakawa Y Ludwiczuk A Nagashima F Chemical Constituents of Bryophytes Bio-and Chemical Diversity Biological Activityand Chemosystematics In Progress in the Chemistry of Organic Natural Products Springer Vienna Austria 2013 Volume 95pp 1ndash796 ISBN 9783709110843

4 Tuba Z Slack NG Stark LR (Eds) Bryophyte Ecology and Climate Change Cambridge University Press Cambridge UK 2011ISBN 978-0-521-75777-5

5 Frahm JP Manual of Topical Bryology Trop Bryol 2003 23 196 [CrossRef]6 Costa DP Nadal F da Rocha TC The First Botanical Explorations of Bryophyte Diversity in the Brazilian Amazon Mountains

High Species Diversity Low Endemism and Low Similarity Biodivers Conserv 2020 29 2663ndash2688 [CrossRef]7 Cannone N Convey P Guglielmin M Diversity Trends of Bryophytes in Continental Antarctica Polar Biol 2013 36 259ndash271

[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

Change In Photosynthesis in Bryophytes and Early Land Plants Hanson DT Rice SK Eds Springer Dordrecht The Netherlands2014 pp 309ndash324 ISBN 978-94-007-6988-5

9 Smith RJ Stark LR Habitat vs Dispersal Constraints on Bryophyte Diversity in the Mojave Desert USA J Arid Environ 2014102 76ndash81 [CrossRef]

10 Stark LR Bisexuality as an Adaptation in Desert Mosses Am Midl Nat 1983 110 445ndash448 [CrossRef]11 Scott GAM Desert Bryophytes In Bryophyte Ecology Smith AJE Ed Springer Dordrecht The Netherlands 1982 pp 105ndash122

ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

39 587ndash596 [CrossRef]14 Ren H Wang F Ye W Zhang Q Han T Huang Y Chu G Hui D Guo Q Bryophyte Diversity Is Related to Vascular

Plant Diversity and Microhabitat under Disturbance in Karst Caves Ecol Indic 2021 120 106947 [CrossRef]15 Von Reuszlig SH Koumlnig WA Olefinic Isothiocyanates and Iminodithiocarbonates from the Liverwort Corsinia coriandrina Eur J

Org Chem 2005 2005 1184ndash1188 [CrossRef]16 Chandra S Chandra D Barh A Pankaj Pandey RK Sharma IP Bryophytes Hoard of Remedies an Ethno-Medicinal

Review J Tradit Complement Med 2016 7 94ndash98 [CrossRef] [PubMed]17 Krishnan VGM Pradeep DP Aswathy JM Krishnan R Lubaina AS Murugan K Wonder Herbals-Bryophytes of

the Ponmudi Hills of Southern Western Ghats Window Into the Need for Conservation World J Pharm Pharm Sci 2014 31548ndash1562

18 Glime J Medical Uses Medical Conditions In Bryophyte Ecology Michigan Technological University Houghton MI USA 2017p 5 Available online httpsdigitalcommonsmtueduoabooks4 (accessed on 6 October 2021)

19 Asakawa Y Biologically Active Compounds from Bryophytes Pure Appl Chem 2007 79 557ndash580 [CrossRef]20 Xie CF Lou HX Secondary Metabolites in Bryophytes An Ecological Aspect Chem Biodivers 2009 6 303ndash312 [CrossRef]21 Asakawa Y Ludwiczuk A Novakovic M Bukvicki D Anchang KY Bis-Bibenzyls Bibenzyls and Terpenoids in 33 Genera

of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

Austria 1982 pp 1ndash28523 Sabovljevic MS Sabovljevic AD Ikram NKK Peramuna A Bae H Simonsen HT BryophytesmdashAn Emerging Source for

Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

110649 [CrossRef]27 Zhu MZ Li Y Zhou JC Lu JH Zhu RX Qiao YN Zhang JZ Zong Y Wang X Jin XY et al Terpenoids from

the Chinese Liverwort Odontoschisma Grosseverrucosum and Their Antifungal Virulence Activity Phytochemistry 2020 174[CrossRef]

28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

41ndash49 [CrossRef]

Agronomy 2022 12 1456 17 of 21

35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

37 Valarezo E Tandazo O Galaacuten K Rosales J Beniacutetez Aacute Volatile Metabolites in Liverworts of Ecuador Metabolites 2020 10 92[CrossRef]

38 Saritas Y Sonwa MM Iznaguen H Koumlnig WA Muhle H Mues R Volatile Constituents in Mosses (Musci) Phytochemistry2001 57 443ndash457 [CrossRef]

39 Tosun G Yaylı B Oumlzdemir T Batan N Bozdeveci A Yaylı N Volatiles and Antimicrobial Activity of the Essential Oils ofthe Mosses Pseudoscleropodium purum Eurhynchium striatum and Eurhynchium angustirete Grown in Turkey Rec Nat Prod 2015 9237ndash242

40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

43 Sakurai K Tomiyama K Kawakami Y Yaguchi Y Asakawa Y Characteristic Scent from the Tahitian Liverwort CyathodiumFoetidissimum J Oleo Sci 2018 67 1265ndash1269 [CrossRef]

44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

45 Asakawa Y Joulain D Chemical Constituents of Unidentified Malaysian Liverwort Astrella () Species J Hattori Bot Lab 1995188 183ndash188 [CrossRef]

46 Toyota M Saito T Matsunami J Asakawa Y A Comparative Study on Three Chemo-Types of the Liverwort ConocephalumConicum Using Volatile Constituents Phytochemistry 1997 44 1265ndash1270 [CrossRef]

47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

48 Ludwiczuk A Komala I Pham A Bianchini JP Raharivelomanana P Asakawa Y Volatile Components from SelectedTahitian Liverworts Nat Prod Commun 2009 4 1387ndash1392 [CrossRef]

49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

51 Pannequin A Tintaru A Desjobert JM Costa J Muselli A New Advances in the Volatile Metabolites of Frullania tamarisciFlavour Fragr J 2017 32 409ndash418 [CrossRef]

52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

64 Vats S Alam A Antibacterial Activity of Atrichum undulatum (Hedw) P Beauv against Some Pathogenic Bacteria J Biol Sci2013 13 427ndash431 [CrossRef]

65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

68 Karpinski TM Adamczak A Antibacterial Activity of Ethanolic Extracts of Some Moss Species Herba Pol 2017 63 11ndash17[CrossRef]

69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

77 Nikolajeva V Liepina L Petrina Z Krumina G Grube M Muiznieks I Antibacterial Activity of Extracts from SomeBryophytes Adv Microbiol 2012 02 345ndash353 [CrossRef]

78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

79 Basile A Giordano S Sorbo S Vuotto ML Ielpo MTL Cobianchi RC Antibiotic Effects of Lunularia cruciata (Bryophyta)Extract Pharm Biol 1998 36 25ndash28 [CrossRef]

80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 9: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)Nees Dumortieraceae Pseudomonas aeruginosa (MIC

64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC125 microgmL)

Bacillus cereus (125 microgmL)Bacillus megaterium (MIC

25 microgmL)Bacillus subtilis (MIC25 microgmL)

Cryptococcus neoformans (MIC125 microgmL) Staphylococcus aureus

(MIC 313ndash25)Salmonella typhimurium (MIC

100 microgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50100 microgmL) [19]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae Streptococcus mutans (LD50

8 microgmL) [19]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdashminimuminhibitory concentration Bold numbers refer to the chemical structures o Bold numbers refer to the chemicalstructures of compounds are presented in Figures 1 and 2

Agronomy 2022 12 x FOR PEER REVIEW 9 of 21

Table 4 Antimicrobial activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Lunularin (6) Dumortiera hirsuta (Sw)

Nees Dumortieraceae Pseudomonas aeruginosa (MIC 64 mgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Acinetobacter cacoaceticus (MIC 125 μgmL)

Bacillus cereus (125 μgmL)

Bacillus megaterium (MIC 25 μgmL)

Bacillus subtilis (MIC25 μgmL)

Cryptococcus neoformans (MIC 125 μgmL)

Staphylococcus aureus (MIC 313ndash25)

Salmonella typhimurium (MIC 100 μgmL)

[8889]

Polygodial (14) Porella vernicosa Lindb Porellaceae Streptococcus mutans (LD50 100 μgmL) [19]

Sacculatal (15) Pellia endiviifolia (Dicks)

Dumort Pelliaceae Streptococcus mutans (LD50 8 μgmL) [19]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae Bacillus subtilis [90]

LD50mdashlethal dose the amount of a compound that it takes to kill 50 of tested pathogen cells MICmdash

minimum inhibitory concentration Bold numbers refer to the chemical structures o Bold numbers

refer to the chemical structures of compounds are presented in Figures 1 and 2

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygo-

dial 15 sacculatal 16 riccardiphenol C)

Apart from their antibacterial potential bryophyte extracts show antifungal proper-

ties The results of the research show that the extracts of certain species of mosses and

liverworts do not exhibit these properties despite their antibacterial effects [737980]

Such selectivity may have industrial or medical applications [4791ndash93] On the other

Figure 2 Chemical structures of compounds mentioned in Table 4 (13 marchantin A 14 polygodial15 sacculatal 16 riccardiphenol C)

Agronomy 2022 12 1456 10 of 21

Apart from their antibacterial potential bryophyte extracts show antifungal proper-ties The results of the research show that the extracts of certain species of mosses andliverworts do not exhibit these properties despite their antibacterial effects [737980] Suchselectivity may have industrial or medical applications [4791ndash93] On the other hand theisolated antifungal substances show activity against numerous pathogenic fungi (Table 5Figure 3) [7588ndash9094ndash97]

Table 5 Antifungal activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Asterelin A (17 R=H)Asterelin B (18 R=Me)

Asterella angusta(Stephani) Pandeacute KPSrivast amp Sultan Khan

Aytoniaceae Candida albicans [94]

Bazzanin B (19 R=Cl)Bazzanin S (20 R=H) Bazzania trilobata L Lepidoziaceae

Botrytis cinerea (IC50 189)Cladosporium cucumerinum (IC50

175)Pyricularia oryzae (IC50 39)

Zymoseptoria tritici (IC50 235)

[75]

Isoplagiochin D (21)Bazzania trilobata LLepidozia incurvata

LindenbLepidoziaceae Zymoseptoria tritici (IC50 159) [95]

Isoriccardin C (22)Plagiochasmaintermedium

Lindenb amp GottscheAytoniaceae Candida albicans [95]

Gymnomitrol (23)Bazzania trilobata L

Gymnomitrion obtusum(Lindb) Pears

LepidoziaceaeGymnomitriaceae

Phytophthora infestansPyricularia oryzae

Zymoseptoria tritici[7598]

Marchantin A (13) Marchantia species L Marchantiaceae

Aspergillus niger (MIC25-100 microgmL)

Pyricularia oryzae (MIC125 microgmL)

Rhizoctonia solani (MIC 50 microgmL)Saccharomyces cerevisiae (MIC

313 microgmL)Trichophyton mentagrophytes (MIC

313 microgmL)

[8889]

Marchantin H (24)

Marchantia polymorphaL

Plagiochasmaintermedium Lindenb amp

Gotische

MarchantiaceaAytoniaceae Candida albicans (MIC 256 microgmL) [97]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorphaL Marchantiaceae Candida albicans [96]

Riccardin C (27)

Asterella angusta(Stephani) Pandeacute KP

Sri-vast amp Sultan KhanPlagiochasma

intermedium Lindenb ampGotische

AytoniaceaeAytoniaceae Candida albicans [97]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Candida albicans

Trichophyton mtagropbytes [90]

IC50 the concentration of a drug that is required for 50 inhibition in vitro MICmdashminimum inhibitory concentra-tion Bold numbers refer to the chemical structures o Bold numbers refer to the chemical structures of compoundsare presented in Figures 2 and 3

Agronomy 2022 12 1456 11 of 21Agronomy 2022 12 x FOR PEER REVIEW 11 of 21

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 asterelin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardin C 23 gym-nomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH 27 riccardin C)

33 Cytotoxic Compounds The bryophyte extracts apart from their antimicrobial activities showed cytotoxic

activities in vitro [387] The same was corroborated for some particular compounds Some of them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 aster-elin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardinC 23 gymnomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH27 riccardin C)

33 Cytotoxic Compounds

The bryophyte extracts apart from their antimicrobial activities showed cytotoxicactivities in vitro [387] The same was corroborated for some particular compounds Someof them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Agronomy 2022 12 1456 12 of 21

PC3 These compounds were tested on several human and mouse tumor lines breast cancerMCF-7 cellosaurus P388 chemoresistant prostate cancer PC3 glioblastoma multiforme U-251 leukemia HL-60 liver cancer HepG2 melanoma RPMI-7951 and monocytic leukemiaU937 (Table 6 Figure 4)

Table 6 Cytotoxic compounds isolated from bryophytes with modern uses

Compounds Species Family Activity Against Ref

Jungermannenone A(28 R=OH)

Jungermannenone B(29 R=H)

Jungermannia species L Jungermanniaceae

Human leukemia HL-60 cells(JA IC50

1 13 microM)PC3 (JA 15 micromolL JB

5 micromolL)

[399]

Lunularin (6) Dumortiera hirsuta (Sw)Nees Weisnerellaceae HepG2 (IC50 = 74 microgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Human MCF-7 breastcancer (IC50 40 microgmL)

chemoresistant prostate cancerPC3 cells

A375 melanoma cells(IC50 = 745ndash1197 microgmL)

[3100101]

Marsupellone (30) Marsupella emarginata(Ehrh) Dumort Gymnomitriaceaea P388 cancer cell line

(ID50 1 microgmL) [88]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorpha LSchistochila glaucescens

(Hook) AEvans

MarchantiaceaeSchistochilaceae P388 cell line (IC50 8ndash18 microgmL) [102]

Pallidisetin A (31)Pallidisetin B (32)

Polytrichum pallidisetumFunck Polytrichaceae

Melanoma (RPMI-7951)Glioblastoma multiforme

(U-251)[103]

Plagiochin E (33) Plagiochasm intermediumLindenb amp Gottsche Aytoniaceae Chemoresistant prostate cancer

PC3 cells (IC50 599 micromolL) [100]

Riccardin C (27)

Plagiochasma intermediumLindenb amp Gottsche

Reboulia hemisphaerica (L)Raddi

Aytoniaceae Chemoresistant prostate cancerPC3 cells (IC50 322 micromolL) [100104]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae BSC cells [90]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae

Human melanoma(IC50 2ndash4 micromolL) Lu1

(IC50 57 micromolL)KB (IC50 32 micromolL)

LNCaP and ZR-75-1 cells(IC50 76 micromolL)

[105]

Trewiasine (34)

Isothecium subdiversiformeBroth

Thamnobryum sandeiBesch

BrachytheciaceaeNeckeraceae

U937 cells ascitic tumors S180hepatoma U14 solid tumor

Lewis lung carcinoma[106]

1 IC50 the concentration of a drug that is required for 50 inhibition of cell growth in vitro Bold numbersrefer to the chemical structures o Bold numbers refer to the chemical structures of compounds are presented inFigures 3 and 4

Agronomy 2022 12 1456 13 of 21Agronomy 2022 12 x FOR PEER REVIEW 13 of 21

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenone B R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds In several species of the Radula Dumort genus cannabinoid compounds have been

discovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated from Radula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor) Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests on mouse brains showed that this compound is bioavailable and selectively binds to CB1 and CB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to Δ9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenoneB R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds

In several species of the Radula Dumort genus cannabinoid compounds have beendiscovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated fromRadula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor)Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests onmouse brains showed that this compound is bioavailable and selectively binds to CB1 andCB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to ∆9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

References1 Cole TCH Hilger HH Goffinet B Bryophyte Phylogeny Poster (BPP) PeerJ Prepr 2019 7 e27571v3 [CrossRef]2 de Sousa F Foster PG Donoghue PCJ Schneider H Cox CJ Nuclear Protein Phylogenies Support the Monophyly of the

Three Bryophyte Groups (Bryophyta Schimp) New Phytol 2019 222 565ndash575 [CrossRef]

Agronomy 2022 12 1456 16 of 21

3 Asakawa Y Ludwiczuk A Nagashima F Chemical Constituents of Bryophytes Bio-and Chemical Diversity Biological Activityand Chemosystematics In Progress in the Chemistry of Organic Natural Products Springer Vienna Austria 2013 Volume 95pp 1ndash796 ISBN 9783709110843

4 Tuba Z Slack NG Stark LR (Eds) Bryophyte Ecology and Climate Change Cambridge University Press Cambridge UK 2011ISBN 978-0-521-75777-5

5 Frahm JP Manual of Topical Bryology Trop Bryol 2003 23 196 [CrossRef]6 Costa DP Nadal F da Rocha TC The First Botanical Explorations of Bryophyte Diversity in the Brazilian Amazon Mountains

High Species Diversity Low Endemism and Low Similarity Biodivers Conserv 2020 29 2663ndash2688 [CrossRef]7 Cannone N Convey P Guglielmin M Diversity Trends of Bryophytes in Continental Antarctica Polar Biol 2013 36 259ndash271

[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

Change In Photosynthesis in Bryophytes and Early Land Plants Hanson DT Rice SK Eds Springer Dordrecht The Netherlands2014 pp 309ndash324 ISBN 978-94-007-6988-5

9 Smith RJ Stark LR Habitat vs Dispersal Constraints on Bryophyte Diversity in the Mojave Desert USA J Arid Environ 2014102 76ndash81 [CrossRef]

10 Stark LR Bisexuality as an Adaptation in Desert Mosses Am Midl Nat 1983 110 445ndash448 [CrossRef]11 Scott GAM Desert Bryophytes In Bryophyte Ecology Smith AJE Ed Springer Dordrecht The Netherlands 1982 pp 105ndash122

ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

39 587ndash596 [CrossRef]14 Ren H Wang F Ye W Zhang Q Han T Huang Y Chu G Hui D Guo Q Bryophyte Diversity Is Related to Vascular

Plant Diversity and Microhabitat under Disturbance in Karst Caves Ecol Indic 2021 120 106947 [CrossRef]15 Von Reuszlig SH Koumlnig WA Olefinic Isothiocyanates and Iminodithiocarbonates from the Liverwort Corsinia coriandrina Eur J

Org Chem 2005 2005 1184ndash1188 [CrossRef]16 Chandra S Chandra D Barh A Pankaj Pandey RK Sharma IP Bryophytes Hoard of Remedies an Ethno-Medicinal

Review J Tradit Complement Med 2016 7 94ndash98 [CrossRef] [PubMed]17 Krishnan VGM Pradeep DP Aswathy JM Krishnan R Lubaina AS Murugan K Wonder Herbals-Bryophytes of

the Ponmudi Hills of Southern Western Ghats Window Into the Need for Conservation World J Pharm Pharm Sci 2014 31548ndash1562

18 Glime J Medical Uses Medical Conditions In Bryophyte Ecology Michigan Technological University Houghton MI USA 2017p 5 Available online httpsdigitalcommonsmtueduoabooks4 (accessed on 6 October 2021)

19 Asakawa Y Biologically Active Compounds from Bryophytes Pure Appl Chem 2007 79 557ndash580 [CrossRef]20 Xie CF Lou HX Secondary Metabolites in Bryophytes An Ecological Aspect Chem Biodivers 2009 6 303ndash312 [CrossRef]21 Asakawa Y Ludwiczuk A Novakovic M Bukvicki D Anchang KY Bis-Bibenzyls Bibenzyls and Terpenoids in 33 Genera

of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

Austria 1982 pp 1ndash28523 Sabovljevic MS Sabovljevic AD Ikram NKK Peramuna A Bae H Simonsen HT BryophytesmdashAn Emerging Source for

Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

110649 [CrossRef]27 Zhu MZ Li Y Zhou JC Lu JH Zhu RX Qiao YN Zhang JZ Zong Y Wang X Jin XY et al Terpenoids from

the Chinese Liverwort Odontoschisma Grosseverrucosum and Their Antifungal Virulence Activity Phytochemistry 2020 174[CrossRef]

28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

41ndash49 [CrossRef]

Agronomy 2022 12 1456 17 of 21

35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

37 Valarezo E Tandazo O Galaacuten K Rosales J Beniacutetez Aacute Volatile Metabolites in Liverworts of Ecuador Metabolites 2020 10 92[CrossRef]

38 Saritas Y Sonwa MM Iznaguen H Koumlnig WA Muhle H Mues R Volatile Constituents in Mosses (Musci) Phytochemistry2001 57 443ndash457 [CrossRef]

39 Tosun G Yaylı B Oumlzdemir T Batan N Bozdeveci A Yaylı N Volatiles and Antimicrobial Activity of the Essential Oils ofthe Mosses Pseudoscleropodium purum Eurhynchium striatum and Eurhynchium angustirete Grown in Turkey Rec Nat Prod 2015 9237ndash242

40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

43 Sakurai K Tomiyama K Kawakami Y Yaguchi Y Asakawa Y Characteristic Scent from the Tahitian Liverwort CyathodiumFoetidissimum J Oleo Sci 2018 67 1265ndash1269 [CrossRef]

44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

45 Asakawa Y Joulain D Chemical Constituents of Unidentified Malaysian Liverwort Astrella () Species J Hattori Bot Lab 1995188 183ndash188 [CrossRef]

46 Toyota M Saito T Matsunami J Asakawa Y A Comparative Study on Three Chemo-Types of the Liverwort ConocephalumConicum Using Volatile Constituents Phytochemistry 1997 44 1265ndash1270 [CrossRef]

47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

48 Ludwiczuk A Komala I Pham A Bianchini JP Raharivelomanana P Asakawa Y Volatile Components from SelectedTahitian Liverworts Nat Prod Commun 2009 4 1387ndash1392 [CrossRef]

49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

51 Pannequin A Tintaru A Desjobert JM Costa J Muselli A New Advances in the Volatile Metabolites of Frullania tamarisciFlavour Fragr J 2017 32 409ndash418 [CrossRef]

52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

64 Vats S Alam A Antibacterial Activity of Atrichum undulatum (Hedw) P Beauv against Some Pathogenic Bacteria J Biol Sci2013 13 427ndash431 [CrossRef]

65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

68 Karpinski TM Adamczak A Antibacterial Activity of Ethanolic Extracts of Some Moss Species Herba Pol 2017 63 11ndash17[CrossRef]

69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

77 Nikolajeva V Liepina L Petrina Z Krumina G Grube M Muiznieks I Antibacterial Activity of Extracts from SomeBryophytes Adv Microbiol 2012 02 345ndash353 [CrossRef]

78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

79 Basile A Giordano S Sorbo S Vuotto ML Ielpo MTL Cobianchi RC Antibiotic Effects of Lunularia cruciata (Bryophyta)Extract Pharm Biol 1998 36 25ndash28 [CrossRef]

80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 10: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 10 of 21

Apart from their antibacterial potential bryophyte extracts show antifungal proper-ties The results of the research show that the extracts of certain species of mosses andliverworts do not exhibit these properties despite their antibacterial effects [737980] Suchselectivity may have industrial or medical applications [4791ndash93] On the other hand theisolated antifungal substances show activity against numerous pathogenic fungi (Table 5Figure 3) [7588ndash9094ndash97]

Table 5 Antifungal activities of compounds isolated from bryophytes

Compounds Species Family Activity Against References

Asterelin A (17 R=H)Asterelin B (18 R=Me)

Asterella angusta(Stephani) Pandeacute KPSrivast amp Sultan Khan

Aytoniaceae Candida albicans [94]

Bazzanin B (19 R=Cl)Bazzanin S (20 R=H) Bazzania trilobata L Lepidoziaceae

Botrytis cinerea (IC50 189)Cladosporium cucumerinum (IC50

175)Pyricularia oryzae (IC50 39)

Zymoseptoria tritici (IC50 235)

[75]

Isoplagiochin D (21)Bazzania trilobata LLepidozia incurvata

LindenbLepidoziaceae Zymoseptoria tritici (IC50 159) [95]

Isoriccardin C (22)Plagiochasmaintermedium

Lindenb amp GottscheAytoniaceae Candida albicans [95]

Gymnomitrol (23)Bazzania trilobata L

Gymnomitrion obtusum(Lindb) Pears

LepidoziaceaeGymnomitriaceae

Phytophthora infestansPyricularia oryzae

Zymoseptoria tritici[7598]

Marchantin A (13) Marchantia species L Marchantiaceae

Aspergillus niger (MIC25-100 microgmL)

Pyricularia oryzae (MIC125 microgmL)

Rhizoctonia solani (MIC 50 microgmL)Saccharomyces cerevisiae (MIC

313 microgmL)Trichophyton mentagrophytes (MIC

313 microgmL)

[8889]

Marchantin H (24)

Marchantia polymorphaL

Plagiochasmaintermedium Lindenb amp

Gotische

MarchantiaceaAytoniaceae Candida albicans (MIC 256 microgmL) [97]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorphaL Marchantiaceae Candida albicans [96]

Riccardin C (27)

Asterella angusta(Stephani) Pandeacute KP

Sri-vast amp Sultan KhanPlagiochasma

intermedium Lindenb ampGotische

AytoniaceaeAytoniaceae Candida albicans [97]

Riccardiphenol C (16) Riccardia crassaSchwaumlgr Aneuraceae Candida albicans

Trichophyton mtagropbytes [90]

IC50 the concentration of a drug that is required for 50 inhibition in vitro MICmdashminimum inhibitory concentra-tion Bold numbers refer to the chemical structures o Bold numbers refer to the chemical structures of compoundsare presented in Figures 2 and 3

Agronomy 2022 12 1456 11 of 21Agronomy 2022 12 x FOR PEER REVIEW 11 of 21

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 asterelin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardin C 23 gym-nomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH 27 riccardin C)

33 Cytotoxic Compounds The bryophyte extracts apart from their antimicrobial activities showed cytotoxic

activities in vitro [387] The same was corroborated for some particular compounds Some of them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 aster-elin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardinC 23 gymnomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH27 riccardin C)

33 Cytotoxic Compounds

The bryophyte extracts apart from their antimicrobial activities showed cytotoxicactivities in vitro [387] The same was corroborated for some particular compounds Someof them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Agronomy 2022 12 1456 12 of 21

PC3 These compounds were tested on several human and mouse tumor lines breast cancerMCF-7 cellosaurus P388 chemoresistant prostate cancer PC3 glioblastoma multiforme U-251 leukemia HL-60 liver cancer HepG2 melanoma RPMI-7951 and monocytic leukemiaU937 (Table 6 Figure 4)

Table 6 Cytotoxic compounds isolated from bryophytes with modern uses

Compounds Species Family Activity Against Ref

Jungermannenone A(28 R=OH)

Jungermannenone B(29 R=H)

Jungermannia species L Jungermanniaceae

Human leukemia HL-60 cells(JA IC50

1 13 microM)PC3 (JA 15 micromolL JB

5 micromolL)

[399]

Lunularin (6) Dumortiera hirsuta (Sw)Nees Weisnerellaceae HepG2 (IC50 = 74 microgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Human MCF-7 breastcancer (IC50 40 microgmL)

chemoresistant prostate cancerPC3 cells

A375 melanoma cells(IC50 = 745ndash1197 microgmL)

[3100101]

Marsupellone (30) Marsupella emarginata(Ehrh) Dumort Gymnomitriaceaea P388 cancer cell line

(ID50 1 microgmL) [88]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorpha LSchistochila glaucescens

(Hook) AEvans

MarchantiaceaeSchistochilaceae P388 cell line (IC50 8ndash18 microgmL) [102]

Pallidisetin A (31)Pallidisetin B (32)

Polytrichum pallidisetumFunck Polytrichaceae

Melanoma (RPMI-7951)Glioblastoma multiforme

(U-251)[103]

Plagiochin E (33) Plagiochasm intermediumLindenb amp Gottsche Aytoniaceae Chemoresistant prostate cancer

PC3 cells (IC50 599 micromolL) [100]

Riccardin C (27)

Plagiochasma intermediumLindenb amp Gottsche

Reboulia hemisphaerica (L)Raddi

Aytoniaceae Chemoresistant prostate cancerPC3 cells (IC50 322 micromolL) [100104]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae BSC cells [90]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae

Human melanoma(IC50 2ndash4 micromolL) Lu1

(IC50 57 micromolL)KB (IC50 32 micromolL)

LNCaP and ZR-75-1 cells(IC50 76 micromolL)

[105]

Trewiasine (34)

Isothecium subdiversiformeBroth

Thamnobryum sandeiBesch

BrachytheciaceaeNeckeraceae

U937 cells ascitic tumors S180hepatoma U14 solid tumor

Lewis lung carcinoma[106]

1 IC50 the concentration of a drug that is required for 50 inhibition of cell growth in vitro Bold numbersrefer to the chemical structures o Bold numbers refer to the chemical structures of compounds are presented inFigures 3 and 4

Agronomy 2022 12 1456 13 of 21Agronomy 2022 12 x FOR PEER REVIEW 13 of 21

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenone B R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds In several species of the Radula Dumort genus cannabinoid compounds have been

discovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated from Radula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor) Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests on mouse brains showed that this compound is bioavailable and selectively binds to CB1 and CB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to Δ9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenoneB R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds

In several species of the Radula Dumort genus cannabinoid compounds have beendiscovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated fromRadula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor)Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests onmouse brains showed that this compound is bioavailable and selectively binds to CB1 andCB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to ∆9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

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Agronomy 2022 12 1456 16 of 21

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[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

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ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

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of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

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Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

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28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

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35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

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40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

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47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

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49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

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Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

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62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

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66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

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70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

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73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

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75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

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80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

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89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

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103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

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110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

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116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 11: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 11 of 21Agronomy 2022 12 x FOR PEER REVIEW 11 of 21

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 asterelin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardin C 23 gym-nomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH 27 riccardin C)

33 Cytotoxic Compounds The bryophyte extracts apart from their antimicrobial activities showed cytotoxic

activities in vitro [387] The same was corroborated for some particular compounds Some of them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Figure 3 Chemical structures of compounds mentioned in Table 5 (17 asterelin A R=H 18 aster-elin B R=Me 19 bazzanin B R=Cl 20 bazzanin S R=H 21 isoplagiochin D 22 isoriccardinC 23 gymnomitrol 24 marchantin H 25 neomarchantin A R=H 26 neomarchantin B R=OH27 riccardin C)

33 Cytotoxic Compounds

The bryophyte extracts apart from their antimicrobial activities showed cytotoxicactivities in vitro [387] The same was corroborated for some particular compounds Someof them showed cytotoxic activities against drug-resistant neoplasms eg prostate cancer

Agronomy 2022 12 1456 12 of 21

PC3 These compounds were tested on several human and mouse tumor lines breast cancerMCF-7 cellosaurus P388 chemoresistant prostate cancer PC3 glioblastoma multiforme U-251 leukemia HL-60 liver cancer HepG2 melanoma RPMI-7951 and monocytic leukemiaU937 (Table 6 Figure 4)

Table 6 Cytotoxic compounds isolated from bryophytes with modern uses

Compounds Species Family Activity Against Ref

Jungermannenone A(28 R=OH)

Jungermannenone B(29 R=H)

Jungermannia species L Jungermanniaceae

Human leukemia HL-60 cells(JA IC50

1 13 microM)PC3 (JA 15 micromolL JB

5 micromolL)

[399]

Lunularin (6) Dumortiera hirsuta (Sw)Nees Weisnerellaceae HepG2 (IC50 = 74 microgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Human MCF-7 breastcancer (IC50 40 microgmL)

chemoresistant prostate cancerPC3 cells

A375 melanoma cells(IC50 = 745ndash1197 microgmL)

[3100101]

Marsupellone (30) Marsupella emarginata(Ehrh) Dumort Gymnomitriaceaea P388 cancer cell line

(ID50 1 microgmL) [88]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorpha LSchistochila glaucescens

(Hook) AEvans

MarchantiaceaeSchistochilaceae P388 cell line (IC50 8ndash18 microgmL) [102]

Pallidisetin A (31)Pallidisetin B (32)

Polytrichum pallidisetumFunck Polytrichaceae

Melanoma (RPMI-7951)Glioblastoma multiforme

(U-251)[103]

Plagiochin E (33) Plagiochasm intermediumLindenb amp Gottsche Aytoniaceae Chemoresistant prostate cancer

PC3 cells (IC50 599 micromolL) [100]

Riccardin C (27)

Plagiochasma intermediumLindenb amp Gottsche

Reboulia hemisphaerica (L)Raddi

Aytoniaceae Chemoresistant prostate cancerPC3 cells (IC50 322 micromolL) [100104]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae BSC cells [90]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae

Human melanoma(IC50 2ndash4 micromolL) Lu1

(IC50 57 micromolL)KB (IC50 32 micromolL)

LNCaP and ZR-75-1 cells(IC50 76 micromolL)

[105]

Trewiasine (34)

Isothecium subdiversiformeBroth

Thamnobryum sandeiBesch

BrachytheciaceaeNeckeraceae

U937 cells ascitic tumors S180hepatoma U14 solid tumor

Lewis lung carcinoma[106]

1 IC50 the concentration of a drug that is required for 50 inhibition of cell growth in vitro Bold numbersrefer to the chemical structures o Bold numbers refer to the chemical structures of compounds are presented inFigures 3 and 4

Agronomy 2022 12 1456 13 of 21Agronomy 2022 12 x FOR PEER REVIEW 13 of 21

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenone B R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds In several species of the Radula Dumort genus cannabinoid compounds have been

discovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated from Radula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor) Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests on mouse brains showed that this compound is bioavailable and selectively binds to CB1 and CB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to Δ9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenoneB R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds

In several species of the Radula Dumort genus cannabinoid compounds have beendiscovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated fromRadula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor)Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests onmouse brains showed that this compound is bioavailable and selectively binds to CB1 andCB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to ∆9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

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3 Asakawa Y Ludwiczuk A Nagashima F Chemical Constituents of Bryophytes Bio-and Chemical Diversity Biological Activityand Chemosystematics In Progress in the Chemistry of Organic Natural Products Springer Vienna Austria 2013 Volume 95pp 1ndash796 ISBN 9783709110843

4 Tuba Z Slack NG Stark LR (Eds) Bryophyte Ecology and Climate Change Cambridge University Press Cambridge UK 2011ISBN 978-0-521-75777-5

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High Species Diversity Low Endemism and Low Similarity Biodivers Conserv 2020 29 2663ndash2688 [CrossRef]7 Cannone N Convey P Guglielmin M Diversity Trends of Bryophytes in Continental Antarctica Polar Biol 2013 36 259ndash271

[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

Change In Photosynthesis in Bryophytes and Early Land Plants Hanson DT Rice SK Eds Springer Dordrecht The Netherlands2014 pp 309ndash324 ISBN 978-94-007-6988-5

9 Smith RJ Stark LR Habitat vs Dispersal Constraints on Bryophyte Diversity in the Mojave Desert USA J Arid Environ 2014102 76ndash81 [CrossRef]

10 Stark LR Bisexuality as an Adaptation in Desert Mosses Am Midl Nat 1983 110 445ndash448 [CrossRef]11 Scott GAM Desert Bryophytes In Bryophyte Ecology Smith AJE Ed Springer Dordrecht The Netherlands 1982 pp 105ndash122

ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

39 587ndash596 [CrossRef]14 Ren H Wang F Ye W Zhang Q Han T Huang Y Chu G Hui D Guo Q Bryophyte Diversity Is Related to Vascular

Plant Diversity and Microhabitat under Disturbance in Karst Caves Ecol Indic 2021 120 106947 [CrossRef]15 Von Reuszlig SH Koumlnig WA Olefinic Isothiocyanates and Iminodithiocarbonates from the Liverwort Corsinia coriandrina Eur J

Org Chem 2005 2005 1184ndash1188 [CrossRef]16 Chandra S Chandra D Barh A Pankaj Pandey RK Sharma IP Bryophytes Hoard of Remedies an Ethno-Medicinal

Review J Tradit Complement Med 2016 7 94ndash98 [CrossRef] [PubMed]17 Krishnan VGM Pradeep DP Aswathy JM Krishnan R Lubaina AS Murugan K Wonder Herbals-Bryophytes of

the Ponmudi Hills of Southern Western Ghats Window Into the Need for Conservation World J Pharm Pharm Sci 2014 31548ndash1562

18 Glime J Medical Uses Medical Conditions In Bryophyte Ecology Michigan Technological University Houghton MI USA 2017p 5 Available online httpsdigitalcommonsmtueduoabooks4 (accessed on 6 October 2021)

19 Asakawa Y Biologically Active Compounds from Bryophytes Pure Appl Chem 2007 79 557ndash580 [CrossRef]20 Xie CF Lou HX Secondary Metabolites in Bryophytes An Ecological Aspect Chem Biodivers 2009 6 303ndash312 [CrossRef]21 Asakawa Y Ludwiczuk A Novakovic M Bukvicki D Anchang KY Bis-Bibenzyls Bibenzyls and Terpenoids in 33 Genera

of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

Austria 1982 pp 1ndash28523 Sabovljevic MS Sabovljevic AD Ikram NKK Peramuna A Bae H Simonsen HT BryophytesmdashAn Emerging Source for

Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

110649 [CrossRef]27 Zhu MZ Li Y Zhou JC Lu JH Zhu RX Qiao YN Zhang JZ Zong Y Wang X Jin XY et al Terpenoids from

the Chinese Liverwort Odontoschisma Grosseverrucosum and Their Antifungal Virulence Activity Phytochemistry 2020 174[CrossRef]

28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

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35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

37 Valarezo E Tandazo O Galaacuten K Rosales J Beniacutetez Aacute Volatile Metabolites in Liverworts of Ecuador Metabolites 2020 10 92[CrossRef]

38 Saritas Y Sonwa MM Iznaguen H Koumlnig WA Muhle H Mues R Volatile Constituents in Mosses (Musci) Phytochemistry2001 57 443ndash457 [CrossRef]

39 Tosun G Yaylı B Oumlzdemir T Batan N Bozdeveci A Yaylı N Volatiles and Antimicrobial Activity of the Essential Oils ofthe Mosses Pseudoscleropodium purum Eurhynchium striatum and Eurhynchium angustirete Grown in Turkey Rec Nat Prod 2015 9237ndash242

40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

43 Sakurai K Tomiyama K Kawakami Y Yaguchi Y Asakawa Y Characteristic Scent from the Tahitian Liverwort CyathodiumFoetidissimum J Oleo Sci 2018 67 1265ndash1269 [CrossRef]

44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

45 Asakawa Y Joulain D Chemical Constituents of Unidentified Malaysian Liverwort Astrella () Species J Hattori Bot Lab 1995188 183ndash188 [CrossRef]

46 Toyota M Saito T Matsunami J Asakawa Y A Comparative Study on Three Chemo-Types of the Liverwort ConocephalumConicum Using Volatile Constituents Phytochemistry 1997 44 1265ndash1270 [CrossRef]

47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

48 Ludwiczuk A Komala I Pham A Bianchini JP Raharivelomanana P Asakawa Y Volatile Components from SelectedTahitian Liverworts Nat Prod Commun 2009 4 1387ndash1392 [CrossRef]

49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

51 Pannequin A Tintaru A Desjobert JM Costa J Muselli A New Advances in the Volatile Metabolites of Frullania tamarisciFlavour Fragr J 2017 32 409ndash418 [CrossRef]

52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

64 Vats S Alam A Antibacterial Activity of Atrichum undulatum (Hedw) P Beauv against Some Pathogenic Bacteria J Biol Sci2013 13 427ndash431 [CrossRef]

65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

68 Karpinski TM Adamczak A Antibacterial Activity of Ethanolic Extracts of Some Moss Species Herba Pol 2017 63 11ndash17[CrossRef]

69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

77 Nikolajeva V Liepina L Petrina Z Krumina G Grube M Muiznieks I Antibacterial Activity of Extracts from SomeBryophytes Adv Microbiol 2012 02 345ndash353 [CrossRef]

78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

79 Basile A Giordano S Sorbo S Vuotto ML Ielpo MTL Cobianchi RC Antibiotic Effects of Lunularia cruciata (Bryophyta)Extract Pharm Biol 1998 36 25ndash28 [CrossRef]

80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 12: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 12 of 21

PC3 These compounds were tested on several human and mouse tumor lines breast cancerMCF-7 cellosaurus P388 chemoresistant prostate cancer PC3 glioblastoma multiforme U-251 leukemia HL-60 liver cancer HepG2 melanoma RPMI-7951 and monocytic leukemiaU937 (Table 6 Figure 4)

Table 6 Cytotoxic compounds isolated from bryophytes with modern uses

Compounds Species Family Activity Against Ref

Jungermannenone A(28 R=OH)

Jungermannenone B(29 R=H)

Jungermannia species L Jungermanniaceae

Human leukemia HL-60 cells(JA IC50

1 13 microM)PC3 (JA 15 micromolL JB

5 micromolL)

[399]

Lunularin (6) Dumortiera hirsuta (Sw)Nees Weisnerellaceae HepG2 (IC50 = 74 microgmL) [87]

Marchantin A (13) Marchantia species L Marchantiaceae

Human MCF-7 breastcancer (IC50 40 microgmL)

chemoresistant prostate cancerPC3 cells

A375 melanoma cells(IC50 = 745ndash1197 microgmL)

[3100101]

Marsupellone (30) Marsupella emarginata(Ehrh) Dumort Gymnomitriaceaea P388 cancer cell line

(ID50 1 microgmL) [88]

Neomarchantin A(25 R=H)

Neomarchantin B(26 R=OH)

Marchantia polymorpha LSchistochila glaucescens

(Hook) AEvans

MarchantiaceaeSchistochilaceae P388 cell line (IC50 8ndash18 microgmL) [102]

Pallidisetin A (31)Pallidisetin B (32)

Polytrichum pallidisetumFunck Polytrichaceae

Melanoma (RPMI-7951)Glioblastoma multiforme

(U-251)[103]

Plagiochin E (33) Plagiochasm intermediumLindenb amp Gottsche Aytoniaceae Chemoresistant prostate cancer

PC3 cells (IC50 599 micromolL) [100]

Riccardin C (27)

Plagiochasma intermediumLindenb amp Gottsche

Reboulia hemisphaerica (L)Raddi

Aytoniaceae Chemoresistant prostate cancerPC3 cells (IC50 322 micromolL) [100104]

Riccardiphenol C (16) Riccardia crassa Schwaumlgr Aneuraceae BSC cells [90]

Sacculatal (15) Pellia endiviifolia(Dicks) Dumort Pelliaceae

Human melanoma(IC50 2ndash4 micromolL) Lu1

(IC50 57 micromolL)KB (IC50 32 micromolL)

LNCaP and ZR-75-1 cells(IC50 76 micromolL)

[105]

Trewiasine (34)

Isothecium subdiversiformeBroth

Thamnobryum sandeiBesch

BrachytheciaceaeNeckeraceae

U937 cells ascitic tumors S180hepatoma U14 solid tumor

Lewis lung carcinoma[106]

1 IC50 the concentration of a drug that is required for 50 inhibition of cell growth in vitro Bold numbersrefer to the chemical structures o Bold numbers refer to the chemical structures of compounds are presented inFigures 3 and 4

Agronomy 2022 12 1456 13 of 21Agronomy 2022 12 x FOR PEER REVIEW 13 of 21

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenone B R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds In several species of the Radula Dumort genus cannabinoid compounds have been

discovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated from Radula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor) Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests on mouse brains showed that this compound is bioavailable and selectively binds to CB1 and CB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to Δ9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenoneB R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds

In several species of the Radula Dumort genus cannabinoid compounds have beendiscovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated fromRadula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor)Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests onmouse brains showed that this compound is bioavailable and selectively binds to CB1 andCB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to ∆9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

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Agronomy 2022 12 1456 16 of 21

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[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

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ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

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the Ponmudi Hills of Southern Western Ghats Window Into the Need for Conservation World J Pharm Pharm Sci 2014 31548ndash1562

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of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

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Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

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28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

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35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

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40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

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44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

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47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

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49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

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52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

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62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

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66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

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70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

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78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

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80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

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89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 13: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 13 of 21Agronomy 2022 12 x FOR PEER REVIEW 13 of 21

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenone B R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds In several species of the Radula Dumort genus cannabinoid compounds have been

discovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated from Radula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor) Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests on mouse brains showed that this compound is bioavailable and selectively binds to CB1 and CB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to Δ9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Figure 4 Compounds mentioned in Table 6 (28 jungermannenone A R=OH 29 jungermannenoneB R=H 30 marsupellone 31 pallidisetin A 32 pallidisetin B 33 plagiochin E 34 trewiasine)

34 Other Compounds

In several species of the Radula Dumort genus cannabinoid compounds have beendiscovered The benzyl cis-THC (-)-perrottetinene (cis-PET) (Figure 5) was isolated fromRadula perrottetii Gottsche ex Stephani [107108] Radula marginata (Hookf amp Taylor)Gottsche Lindenb amp Nees [108109] and Radula laxiramea Steph [108110] Tests onmouse brains showed that this compound is bioavailable and selectively binds to CB1 andCB2 receptors at nanomolar concentrations in vitro Cis-PET induced similar effects to ∆9ndashtrans-THC including antinociception hypothermia catalepsy and hypolocomotion [111]

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

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3 Asakawa Y Ludwiczuk A Nagashima F Chemical Constituents of Bryophytes Bio-and Chemical Diversity Biological Activityand Chemosystematics In Progress in the Chemistry of Organic Natural Products Springer Vienna Austria 2013 Volume 95pp 1ndash796 ISBN 9783709110843

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[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

Change In Photosynthesis in Bryophytes and Early Land Plants Hanson DT Rice SK Eds Springer Dordrecht The Netherlands2014 pp 309ndash324 ISBN 978-94-007-6988-5

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ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

39 587ndash596 [CrossRef]14 Ren H Wang F Ye W Zhang Q Han T Huang Y Chu G Hui D Guo Q Bryophyte Diversity Is Related to Vascular

Plant Diversity and Microhabitat under Disturbance in Karst Caves Ecol Indic 2021 120 106947 [CrossRef]15 Von Reuszlig SH Koumlnig WA Olefinic Isothiocyanates and Iminodithiocarbonates from the Liverwort Corsinia coriandrina Eur J

Org Chem 2005 2005 1184ndash1188 [CrossRef]16 Chandra S Chandra D Barh A Pankaj Pandey RK Sharma IP Bryophytes Hoard of Remedies an Ethno-Medicinal

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the Ponmudi Hills of Southern Western Ghats Window Into the Need for Conservation World J Pharm Pharm Sci 2014 31548ndash1562

18 Glime J Medical Uses Medical Conditions In Bryophyte Ecology Michigan Technological University Houghton MI USA 2017p 5 Available online httpsdigitalcommonsmtueduoabooks4 (accessed on 6 October 2021)

19 Asakawa Y Biologically Active Compounds from Bryophytes Pure Appl Chem 2007 79 557ndash580 [CrossRef]20 Xie CF Lou HX Secondary Metabolites in Bryophytes An Ecological Aspect Chem Biodivers 2009 6 303ndash312 [CrossRef]21 Asakawa Y Ludwiczuk A Novakovic M Bukvicki D Anchang KY Bis-Bibenzyls Bibenzyls and Terpenoids in 33 Genera

of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

Austria 1982 pp 1ndash28523 Sabovljevic MS Sabovljevic AD Ikram NKK Peramuna A Bae H Simonsen HT BryophytesmdashAn Emerging Source for

Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

110649 [CrossRef]27 Zhu MZ Li Y Zhou JC Lu JH Zhu RX Qiao YN Zhang JZ Zong Y Wang X Jin XY et al Terpenoids from

the Chinese Liverwort Odontoschisma Grosseverrucosum and Their Antifungal Virulence Activity Phytochemistry 2020 174[CrossRef]

28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

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35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

37 Valarezo E Tandazo O Galaacuten K Rosales J Beniacutetez Aacute Volatile Metabolites in Liverworts of Ecuador Metabolites 2020 10 92[CrossRef]

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39 Tosun G Yaylı B Oumlzdemir T Batan N Bozdeveci A Yaylı N Volatiles and Antimicrobial Activity of the Essential Oils ofthe Mosses Pseudoscleropodium purum Eurhynchium striatum and Eurhynchium angustirete Grown in Turkey Rec Nat Prod 2015 9237ndash242

40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

43 Sakurai K Tomiyama K Kawakami Y Yaguchi Y Asakawa Y Characteristic Scent from the Tahitian Liverwort CyathodiumFoetidissimum J Oleo Sci 2018 67 1265ndash1269 [CrossRef]

44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

45 Asakawa Y Joulain D Chemical Constituents of Unidentified Malaysian Liverwort Astrella () Species J Hattori Bot Lab 1995188 183ndash188 [CrossRef]

46 Toyota M Saito T Matsunami J Asakawa Y A Comparative Study on Three Chemo-Types of the Liverwort ConocephalumConicum Using Volatile Constituents Phytochemistry 1997 44 1265ndash1270 [CrossRef]

47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

48 Ludwiczuk A Komala I Pham A Bianchini JP Raharivelomanana P Asakawa Y Volatile Components from SelectedTahitian Liverworts Nat Prod Commun 2009 4 1387ndash1392 [CrossRef]

49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

51 Pannequin A Tintaru A Desjobert JM Costa J Muselli A New Advances in the Volatile Metabolites of Frullania tamarisciFlavour Fragr J 2017 32 409ndash418 [CrossRef]

52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

64 Vats S Alam A Antibacterial Activity of Atrichum undulatum (Hedw) P Beauv against Some Pathogenic Bacteria J Biol Sci2013 13 427ndash431 [CrossRef]

65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

68 Karpinski TM Adamczak A Antibacterial Activity of Ethanolic Extracts of Some Moss Species Herba Pol 2017 63 11ndash17[CrossRef]

69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

77 Nikolajeva V Liepina L Petrina Z Krumina G Grube M Muiznieks I Antibacterial Activity of Extracts from SomeBryophytes Adv Microbiol 2012 02 345ndash353 [CrossRef]

78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

79 Basile A Giordano S Sorbo S Vuotto ML Ielpo MTL Cobianchi RC Antibiotic Effects of Lunularia cruciata (Bryophyta)Extract Pharm Biol 1998 36 25ndash28 [CrossRef]

80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 14: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 14 of 21Agronomy 2022 12 x FOR PEER REVIEW 14 of 21

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used in

medicine and in industry However the isolation of secondary metabolites requires large

amounts of plant material Harvesting from nature can negatively affect the environment

and contribute to the loss of biodiversity one of the biggest concerns of the modern world

In vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports

of successful culture induction date back to 1906 [112] and 1913 [113] while the article

describing the first seed plant culture appeared in 1925 [114] The advantages of tissue

cultures in the cultivation of mosses are the ease of obtaining aseptic spores and in the

case of liverworts the vegetative regenerative potential The next milestone was the

identification of environmental conditions stimulating the development of explants

Significant factors were photoperiod light intensity medium composition and air

temperature [115] The conditions favoring the production of secondary metabolites are

equally important Becker [116] described that the qualitative and quantitative

compositions of bryophytes grown in tissue cultures under certain conditions

corresponded to those of bryophytes obtained from the natural environment justifying

the mass production of secondary metabolites from this group of plants eg in

photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating

secondary metabolites from them was developed by Sabovljevic et al [117] This

publication describes the recommended media parameters and culture conditions

appropriate for a given stage of culture The paper touches upon aspects of sterilization

of gametophytes and sporophytes spore germination establishing primary and

secondary protonema multiplication bud induction liquid cultures preparation of

bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In this

context Bryophyta cultures kept in bioreactors are used and secrete metabolites into

culture media Studies have shown that bryophytes produce secondary metabolites in

vitro in similar quantities and of similar quality to bryophytes obtained from the natural

environment The concentration of produced metabolites changes during seasons [118]

Therefore optimization of the micro-reproduction process and the determination of

physical and chemical conditions will allow for the stable and effective production of

secondary metabolites Moreover plant material from in vitro cultures is devoid of

endophytic microorganisms that may distort the results of research conducted on

bryophyte extracts [119120121]

Figure 5 Chemical structures of perrottetinene (35) and tetrahydrocannabinol (THC 36)

4 Bryophytes in Tissue Cultures

A large number of compounds isolated in extracts have the potential to be used inmedicine and in industry However the isolation of secondary metabolites requires largeamounts of plant material Harvesting from nature can negatively affect the environmentand contribute to the loss of biodiversity one of the biggest concerns of the modern worldIn vitro cultures may be a solution to this problem

The history of in vitro cultures of bryophytes is over 100 years old The first reports ofsuccessful culture induction date back to 1906 [112] and 1913 [113] while the article describ-ing the first seed plant culture appeared in 1925 [114] The advantages of tissue cultures inthe cultivation of mosses are the ease of obtaining aseptic spores and in the case of liver-worts the vegetative regenerative potential The next milestone was the identification ofenvironmental conditions stimulating the development of explants Significant factors werephotoperiod light intensity medium composition and air temperature [115] The condi-tions favoring the production of secondary metabolites are equally important Becker [116]described that the qualitative and quantitative compositions of bryophytes grown in tissuecultures under certain conditions corresponded to those of bryophytes obtained from thenatural environment justifying the mass production of secondary metabolites from thisgroup of plants eg in photobioreactors

The methodology of growing bryophytes in in vitro conditions and isolating secondarymetabolites from them was developed by Sabovljevic et al [117] This publication describesthe recommended media parameters and culture conditions appropriate for a given stage ofculture The paper touches upon aspects of sterilization of gametophytes and sporophytesspore germination establishing primary and secondary protonema multiplication budinduction liquid cultures preparation of bryophyte extracts and HPLC analysis

Another set of means of obtaining metabolites are biotechnological methods In thiscontext Bryophyta cultures kept in bioreactors are used and secrete metabolites into culturemedia Studies have shown that bryophytes produce secondary metabolites in vitro in sim-ilar quantities and of similar quality to bryophytes obtained from the natural environmentThe concentration of produced metabolites changes during seasons [118] Therefore opti-mization of the micro-reproduction process and the determination of physical and chemicalconditions will allow for the stable and effective production of secondary metabolitesMoreover plant material from in vitro cultures is devoid of endophytic microorganismsthat may distort the results of research conducted on bryophyte extracts [119ndash121]

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

References1 Cole TCH Hilger HH Goffinet B Bryophyte Phylogeny Poster (BPP) PeerJ Prepr 2019 7 e27571v3 [CrossRef]2 de Sousa F Foster PG Donoghue PCJ Schneider H Cox CJ Nuclear Protein Phylogenies Support the Monophyly of the

Three Bryophyte Groups (Bryophyta Schimp) New Phytol 2019 222 565ndash575 [CrossRef]

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3 Asakawa Y Ludwiczuk A Nagashima F Chemical Constituents of Bryophytes Bio-and Chemical Diversity Biological Activityand Chemosystematics In Progress in the Chemistry of Organic Natural Products Springer Vienna Austria 2013 Volume 95pp 1ndash796 ISBN 9783709110843

4 Tuba Z Slack NG Stark LR (Eds) Bryophyte Ecology and Climate Change Cambridge University Press Cambridge UK 2011ISBN 978-0-521-75777-5

5 Frahm JP Manual of Topical Bryology Trop Bryol 2003 23 196 [CrossRef]6 Costa DP Nadal F da Rocha TC The First Botanical Explorations of Bryophyte Diversity in the Brazilian Amazon Mountains

High Species Diversity Low Endemism and Low Similarity Biodivers Conserv 2020 29 2663ndash2688 [CrossRef]7 Cannone N Convey P Guglielmin M Diversity Trends of Bryophytes in Continental Antarctica Polar Biol 2013 36 259ndash271

[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

Change In Photosynthesis in Bryophytes and Early Land Plants Hanson DT Rice SK Eds Springer Dordrecht The Netherlands2014 pp 309ndash324 ISBN 978-94-007-6988-5

9 Smith RJ Stark LR Habitat vs Dispersal Constraints on Bryophyte Diversity in the Mojave Desert USA J Arid Environ 2014102 76ndash81 [CrossRef]

10 Stark LR Bisexuality as an Adaptation in Desert Mosses Am Midl Nat 1983 110 445ndash448 [CrossRef]11 Scott GAM Desert Bryophytes In Bryophyte Ecology Smith AJE Ed Springer Dordrecht The Netherlands 1982 pp 105ndash122

ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

39 587ndash596 [CrossRef]14 Ren H Wang F Ye W Zhang Q Han T Huang Y Chu G Hui D Guo Q Bryophyte Diversity Is Related to Vascular

Plant Diversity and Microhabitat under Disturbance in Karst Caves Ecol Indic 2021 120 106947 [CrossRef]15 Von Reuszlig SH Koumlnig WA Olefinic Isothiocyanates and Iminodithiocarbonates from the Liverwort Corsinia coriandrina Eur J

Org Chem 2005 2005 1184ndash1188 [CrossRef]16 Chandra S Chandra D Barh A Pankaj Pandey RK Sharma IP Bryophytes Hoard of Remedies an Ethno-Medicinal

Review J Tradit Complement Med 2016 7 94ndash98 [CrossRef] [PubMed]17 Krishnan VGM Pradeep DP Aswathy JM Krishnan R Lubaina AS Murugan K Wonder Herbals-Bryophytes of

the Ponmudi Hills of Southern Western Ghats Window Into the Need for Conservation World J Pharm Pharm Sci 2014 31548ndash1562

18 Glime J Medical Uses Medical Conditions In Bryophyte Ecology Michigan Technological University Houghton MI USA 2017p 5 Available online httpsdigitalcommonsmtueduoabooks4 (accessed on 6 October 2021)

19 Asakawa Y Biologically Active Compounds from Bryophytes Pure Appl Chem 2007 79 557ndash580 [CrossRef]20 Xie CF Lou HX Secondary Metabolites in Bryophytes An Ecological Aspect Chem Biodivers 2009 6 303ndash312 [CrossRef]21 Asakawa Y Ludwiczuk A Novakovic M Bukvicki D Anchang KY Bis-Bibenzyls Bibenzyls and Terpenoids in 33 Genera

of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

Austria 1982 pp 1ndash28523 Sabovljevic MS Sabovljevic AD Ikram NKK Peramuna A Bae H Simonsen HT BryophytesmdashAn Emerging Source for

Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

110649 [CrossRef]27 Zhu MZ Li Y Zhou JC Lu JH Zhu RX Qiao YN Zhang JZ Zong Y Wang X Jin XY et al Terpenoids from

the Chinese Liverwort Odontoschisma Grosseverrucosum and Their Antifungal Virulence Activity Phytochemistry 2020 174[CrossRef]

28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

41ndash49 [CrossRef]

Agronomy 2022 12 1456 17 of 21

35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

37 Valarezo E Tandazo O Galaacuten K Rosales J Beniacutetez Aacute Volatile Metabolites in Liverworts of Ecuador Metabolites 2020 10 92[CrossRef]

38 Saritas Y Sonwa MM Iznaguen H Koumlnig WA Muhle H Mues R Volatile Constituents in Mosses (Musci) Phytochemistry2001 57 443ndash457 [CrossRef]

39 Tosun G Yaylı B Oumlzdemir T Batan N Bozdeveci A Yaylı N Volatiles and Antimicrobial Activity of the Essential Oils ofthe Mosses Pseudoscleropodium purum Eurhynchium striatum and Eurhynchium angustirete Grown in Turkey Rec Nat Prod 2015 9237ndash242

40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

43 Sakurai K Tomiyama K Kawakami Y Yaguchi Y Asakawa Y Characteristic Scent from the Tahitian Liverwort CyathodiumFoetidissimum J Oleo Sci 2018 67 1265ndash1269 [CrossRef]

44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

45 Asakawa Y Joulain D Chemical Constituents of Unidentified Malaysian Liverwort Astrella () Species J Hattori Bot Lab 1995188 183ndash188 [CrossRef]

46 Toyota M Saito T Matsunami J Asakawa Y A Comparative Study on Three Chemo-Types of the Liverwort ConocephalumConicum Using Volatile Constituents Phytochemistry 1997 44 1265ndash1270 [CrossRef]

47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

48 Ludwiczuk A Komala I Pham A Bianchini JP Raharivelomanana P Asakawa Y Volatile Components from SelectedTahitian Liverworts Nat Prod Commun 2009 4 1387ndash1392 [CrossRef]

49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

51 Pannequin A Tintaru A Desjobert JM Costa J Muselli A New Advances in the Volatile Metabolites of Frullania tamarisciFlavour Fragr J 2017 32 409ndash418 [CrossRef]

52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

64 Vats S Alam A Antibacterial Activity of Atrichum undulatum (Hedw) P Beauv against Some Pathogenic Bacteria J Biol Sci2013 13 427ndash431 [CrossRef]

65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

68 Karpinski TM Adamczak A Antibacterial Activity of Ethanolic Extracts of Some Moss Species Herba Pol 2017 63 11ndash17[CrossRef]

69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

77 Nikolajeva V Liepina L Petrina Z Krumina G Grube M Muiznieks I Antibacterial Activity of Extracts from SomeBryophytes Adv Microbiol 2012 02 345ndash353 [CrossRef]

78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

79 Basile A Giordano S Sorbo S Vuotto ML Ielpo MTL Cobianchi RC Antibiotic Effects of Lunularia cruciata (Bryophyta)Extract Pharm Biol 1998 36 25ndash28 [CrossRef]

80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 15: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 15 of 21

5 Conclusions

Bryophytes are important for biodiversity and other ecosystem services They canretain huge amounts of water and therefore act as moisture buffers in many ecosystems [94]and may be used in the management of stormwater [122] They also provide habitatsfor many microorganisms and invertebrates [123124] Cyanobacteria symbiotic withbryophytes assimilate atmospheric nitrogen [125ndash127] which is especially important duringthe process of primary succession [128129] Due to their potential for capture of largeamounts of particulate matter from air both organic [130131] and inorganic [132] they canbe used for monitoring air pollution [133134]

Bryophytes are also a valuable source of biologically active compounds useful inmedicine pharmacy and in industry Their full potential has not been recognized yet Newmetabolites characteristic of this group of plants are still under research Among themmany antibacterial (Table 5) antifungal (Table 6) and cytotoxic compounds can be men-tioned They can offer solutions to increasing pathogen resistance and be used against can-cer target lines Metabolites such as marchantin A plagochilin E and riccardin C exhibit cy-totoxic activities against chemoresistant prostate cancer [3100] In addition to the aforemen-tioned active compounds those with antioxidant [135ndash137] anti-inflammatory [138ndash140]psychoactive [111] antiviral [141] muscle-relaxing [142] neuroprotective [142143] anti-HIV [144] and insecticidal activities can be distinguished [145146] Compounds withnematicidal activity have potential in agricultural industry as natural plant-protectionproducts Some volatile compounds can be used as repellents eg polygodial (30) showsstronger repellent activity against mosquitoes than commercial products [24] Specificaromatic compounds (Table 2) obtained from bryophytes can be used in perfumery andpharmacy Additionally the optimization of production conditions will allow the maxi-mization of the production of secondary metabolites by bryophytes The methodology forthe extraction and isolation of metabolites from bryophytes was described by Asakawaand Ludwiczuk [147] For a less detailed extraction instruction but including directions forHPLC analysis see Sabovljevic et al [117]

Obtaining plant material from nature is problematic due to the degradation of ecosys-tems However it is now possible to reproduce bryophytes massively with less environ-mental impact For this purpose in vitro cultures can be used which enable the massproduction of biomass with the use of various types of photobioreactors [91] There areseveral articles describing the practicalities and problems of in vitro bryophyte cultiva-tion [148ndash150] The optimization of production conditions will maximize production ofsecondary metabolites by bryophytes

To conclude in the last 40 years knowledge of bryophytes has significantly deepenedCurrently scientists are discovering new unique compounds with potential for practicaluse which in the age of drug resistance may be of considerable importance Furtherresearch will allow the determination of the real therapeutic value of these metabolites

Author Contributions Conceptualization KW MD and AS writingmdashoriginal draft preparationMD writingmdashreview and editing KW supervision AS and RG All authors have read andagreed to the published version of the manuscript

Funding The APCBPC is financed by Wroclaw University of Environmental and Life Sciences

Institutional Review Board Statement Not applicable

Informed Consent Statement Not applicable

Data Availability Statement Not applicable

Conflicts of Interest The authors declare no conflict of interest

References1 Cole TCH Hilger HH Goffinet B Bryophyte Phylogeny Poster (BPP) PeerJ Prepr 2019 7 e27571v3 [CrossRef]2 de Sousa F Foster PG Donoghue PCJ Schneider H Cox CJ Nuclear Protein Phylogenies Support the Monophyly of the

Three Bryophyte Groups (Bryophyta Schimp) New Phytol 2019 222 565ndash575 [CrossRef]

Agronomy 2022 12 1456 16 of 21

3 Asakawa Y Ludwiczuk A Nagashima F Chemical Constituents of Bryophytes Bio-and Chemical Diversity Biological Activityand Chemosystematics In Progress in the Chemistry of Organic Natural Products Springer Vienna Austria 2013 Volume 95pp 1ndash796 ISBN 9783709110843

4 Tuba Z Slack NG Stark LR (Eds) Bryophyte Ecology and Climate Change Cambridge University Press Cambridge UK 2011ISBN 978-0-521-75777-5

5 Frahm JP Manual of Topical Bryology Trop Bryol 2003 23 196 [CrossRef]6 Costa DP Nadal F da Rocha TC The First Botanical Explorations of Bryophyte Diversity in the Brazilian Amazon Mountains

High Species Diversity Low Endemism and Low Similarity Biodivers Conserv 2020 29 2663ndash2688 [CrossRef]7 Cannone N Convey P Guglielmin M Diversity Trends of Bryophytes in Continental Antarctica Polar Biol 2013 36 259ndash271

[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

Change In Photosynthesis in Bryophytes and Early Land Plants Hanson DT Rice SK Eds Springer Dordrecht The Netherlands2014 pp 309ndash324 ISBN 978-94-007-6988-5

9 Smith RJ Stark LR Habitat vs Dispersal Constraints on Bryophyte Diversity in the Mojave Desert USA J Arid Environ 2014102 76ndash81 [CrossRef]

10 Stark LR Bisexuality as an Adaptation in Desert Mosses Am Midl Nat 1983 110 445ndash448 [CrossRef]11 Scott GAM Desert Bryophytes In Bryophyte Ecology Smith AJE Ed Springer Dordrecht The Netherlands 1982 pp 105ndash122

ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

39 587ndash596 [CrossRef]14 Ren H Wang F Ye W Zhang Q Han T Huang Y Chu G Hui D Guo Q Bryophyte Diversity Is Related to Vascular

Plant Diversity and Microhabitat under Disturbance in Karst Caves Ecol Indic 2021 120 106947 [CrossRef]15 Von Reuszlig SH Koumlnig WA Olefinic Isothiocyanates and Iminodithiocarbonates from the Liverwort Corsinia coriandrina Eur J

Org Chem 2005 2005 1184ndash1188 [CrossRef]16 Chandra S Chandra D Barh A Pankaj Pandey RK Sharma IP Bryophytes Hoard of Remedies an Ethno-Medicinal

Review J Tradit Complement Med 2016 7 94ndash98 [CrossRef] [PubMed]17 Krishnan VGM Pradeep DP Aswathy JM Krishnan R Lubaina AS Murugan K Wonder Herbals-Bryophytes of

the Ponmudi Hills of Southern Western Ghats Window Into the Need for Conservation World J Pharm Pharm Sci 2014 31548ndash1562

18 Glime J Medical Uses Medical Conditions In Bryophyte Ecology Michigan Technological University Houghton MI USA 2017p 5 Available online httpsdigitalcommonsmtueduoabooks4 (accessed on 6 October 2021)

19 Asakawa Y Biologically Active Compounds from Bryophytes Pure Appl Chem 2007 79 557ndash580 [CrossRef]20 Xie CF Lou HX Secondary Metabolites in Bryophytes An Ecological Aspect Chem Biodivers 2009 6 303ndash312 [CrossRef]21 Asakawa Y Ludwiczuk A Novakovic M Bukvicki D Anchang KY Bis-Bibenzyls Bibenzyls and Terpenoids in 33 Genera

of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

Austria 1982 pp 1ndash28523 Sabovljevic MS Sabovljevic AD Ikram NKK Peramuna A Bae H Simonsen HT BryophytesmdashAn Emerging Source for

Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

110649 [CrossRef]27 Zhu MZ Li Y Zhou JC Lu JH Zhu RX Qiao YN Zhang JZ Zong Y Wang X Jin XY et al Terpenoids from

the Chinese Liverwort Odontoschisma Grosseverrucosum and Their Antifungal Virulence Activity Phytochemistry 2020 174[CrossRef]

28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

41ndash49 [CrossRef]

Agronomy 2022 12 1456 17 of 21

35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

37 Valarezo E Tandazo O Galaacuten K Rosales J Beniacutetez Aacute Volatile Metabolites in Liverworts of Ecuador Metabolites 2020 10 92[CrossRef]

38 Saritas Y Sonwa MM Iznaguen H Koumlnig WA Muhle H Mues R Volatile Constituents in Mosses (Musci) Phytochemistry2001 57 443ndash457 [CrossRef]

39 Tosun G Yaylı B Oumlzdemir T Batan N Bozdeveci A Yaylı N Volatiles and Antimicrobial Activity of the Essential Oils ofthe Mosses Pseudoscleropodium purum Eurhynchium striatum and Eurhynchium angustirete Grown in Turkey Rec Nat Prod 2015 9237ndash242

40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

43 Sakurai K Tomiyama K Kawakami Y Yaguchi Y Asakawa Y Characteristic Scent from the Tahitian Liverwort CyathodiumFoetidissimum J Oleo Sci 2018 67 1265ndash1269 [CrossRef]

44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

45 Asakawa Y Joulain D Chemical Constituents of Unidentified Malaysian Liverwort Astrella () Species J Hattori Bot Lab 1995188 183ndash188 [CrossRef]

46 Toyota M Saito T Matsunami J Asakawa Y A Comparative Study on Three Chemo-Types of the Liverwort ConocephalumConicum Using Volatile Constituents Phytochemistry 1997 44 1265ndash1270 [CrossRef]

47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

48 Ludwiczuk A Komala I Pham A Bianchini JP Raharivelomanana P Asakawa Y Volatile Components from SelectedTahitian Liverworts Nat Prod Commun 2009 4 1387ndash1392 [CrossRef]

49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

51 Pannequin A Tintaru A Desjobert JM Costa J Muselli A New Advances in the Volatile Metabolites of Frullania tamarisciFlavour Fragr J 2017 32 409ndash418 [CrossRef]

52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

64 Vats S Alam A Antibacterial Activity of Atrichum undulatum (Hedw) P Beauv against Some Pathogenic Bacteria J Biol Sci2013 13 427ndash431 [CrossRef]

65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

68 Karpinski TM Adamczak A Antibacterial Activity of Ethanolic Extracts of Some Moss Species Herba Pol 2017 63 11ndash17[CrossRef]

69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

77 Nikolajeva V Liepina L Petrina Z Krumina G Grube M Muiznieks I Antibacterial Activity of Extracts from SomeBryophytes Adv Microbiol 2012 02 345ndash353 [CrossRef]

78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

79 Basile A Giordano S Sorbo S Vuotto ML Ielpo MTL Cobianchi RC Antibiotic Effects of Lunularia cruciata (Bryophyta)Extract Pharm Biol 1998 36 25ndash28 [CrossRef]

80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 16: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 16 of 21

3 Asakawa Y Ludwiczuk A Nagashima F Chemical Constituents of Bryophytes Bio-and Chemical Diversity Biological Activityand Chemosystematics In Progress in the Chemistry of Organic Natural Products Springer Vienna Austria 2013 Volume 95pp 1ndash796 ISBN 9783709110843

4 Tuba Z Slack NG Stark LR (Eds) Bryophyte Ecology and Climate Change Cambridge University Press Cambridge UK 2011ISBN 978-0-521-75777-5

5 Frahm JP Manual of Topical Bryology Trop Bryol 2003 23 196 [CrossRef]6 Costa DP Nadal F da Rocha TC The First Botanical Explorations of Bryophyte Diversity in the Brazilian Amazon Mountains

High Species Diversity Low Endemism and Low Similarity Biodivers Conserv 2020 29 2663ndash2688 [CrossRef]7 Cannone N Convey P Guglielmin M Diversity Trends of Bryophytes in Continental Antarctica Polar Biol 2013 36 259ndash271

[CrossRef]8 Bramley-Alves J King DH Robinson SA Miller RE Dominating the Antarctic Environment Bryophytes in a Time of

Change In Photosynthesis in Bryophytes and Early Land Plants Hanson DT Rice SK Eds Springer Dordrecht The Netherlands2014 pp 309ndash324 ISBN 978-94-007-6988-5

9 Smith RJ Stark LR Habitat vs Dispersal Constraints on Bryophyte Diversity in the Mojave Desert USA J Arid Environ 2014102 76ndash81 [CrossRef]

10 Stark LR Bisexuality as an Adaptation in Desert Mosses Am Midl Nat 1983 110 445ndash448 [CrossRef]11 Scott GAM Desert Bryophytes In Bryophyte Ecology Smith AJE Ed Springer Dordrecht The Netherlands 1982 pp 105ndash122

ISBN 978-94-009-5891-312 Mežaka A Suško U Opmanis A Distribution of Schistostega pennata in Latvia Folia Cryptogam Est 2011 63 59ndash6313 Mulec J Kubešova S Diversity of Bryophytes in Show Caves in Slovenia and Relation to Light Intensities Acta Carsologica 2010

39 587ndash596 [CrossRef]14 Ren H Wang F Ye W Zhang Q Han T Huang Y Chu G Hui D Guo Q Bryophyte Diversity Is Related to Vascular

Plant Diversity and Microhabitat under Disturbance in Karst Caves Ecol Indic 2021 120 106947 [CrossRef]15 Von Reuszlig SH Koumlnig WA Olefinic Isothiocyanates and Iminodithiocarbonates from the Liverwort Corsinia coriandrina Eur J

Org Chem 2005 2005 1184ndash1188 [CrossRef]16 Chandra S Chandra D Barh A Pankaj Pandey RK Sharma IP Bryophytes Hoard of Remedies an Ethno-Medicinal

Review J Tradit Complement Med 2016 7 94ndash98 [CrossRef] [PubMed]17 Krishnan VGM Pradeep DP Aswathy JM Krishnan R Lubaina AS Murugan K Wonder Herbals-Bryophytes of

the Ponmudi Hills of Southern Western Ghats Window Into the Need for Conservation World J Pharm Pharm Sci 2014 31548ndash1562

18 Glime J Medical Uses Medical Conditions In Bryophyte Ecology Michigan Technological University Houghton MI USA 2017p 5 Available online httpsdigitalcommonsmtueduoabooks4 (accessed on 6 October 2021)

19 Asakawa Y Biologically Active Compounds from Bryophytes Pure Appl Chem 2007 79 557ndash580 [CrossRef]20 Xie CF Lou HX Secondary Metabolites in Bryophytes An Ecological Aspect Chem Biodivers 2009 6 303ndash312 [CrossRef]21 Asakawa Y Ludwiczuk A Novakovic M Bukvicki D Anchang KY Bis-Bibenzyls Bibenzyls and Terpenoids in 33 Genera

of the Marchantiophyta (Liverworts) Structures Synthesis and Bioactivity J Nat Prod 2022 85 729ndash762 [CrossRef]22 Asakawa Y Chemical Constituents of the Hepaticae In Progress in the Chemistry of Organic Natural Products Springer Vienna

Austria 1982 pp 1ndash28523 Sabovljevic MS Sabovljevic AD Ikram NKK Peramuna A Bae H Simonsen HT BryophytesmdashAn Emerging Source for

Herbal Remedies and Chemical Production Plant Genet Resour Characterisation Util 2016 14 314ndash327 [CrossRef]24 Asakawa Y Chemical Constituents of Bryophytes In Progress in the Chemistry of Organic Natural Products Herz W Kirby WG

Moore RE Steglich W Tamm C Eds Springer Wein Austria 1995 pp 1ndash61825 Glime JM Bryophytes and Herbivory Cryptogam Bryol 2006 27 191ndash20326 Ludwiczuk A Asakawa Y Bryophytes as a Source of Bioactive Volatile TerpenoidsmdashA Review Food Chem Toxicol 2019 132

110649 [CrossRef]27 Zhu MZ Li Y Zhou JC Lu JH Zhu RX Qiao YN Zhang JZ Zong Y Wang X Jin XY et al Terpenoids from

the Chinese Liverwort Odontoschisma Grosseverrucosum and Their Antifungal Virulence Activity Phytochemistry 2020 174[CrossRef]

28 Alam A Shrama V Rawat KK Verma PK BryophytesmdashThe Ignored Medicinal Plants SMU Med J 2014 2 299ndash31729 Hernaacutendez-Rodriacuteguez E Delgadillo-Moya C The Ethnobotany of Bryophytes in Mexico Bot Sci 2021 99 13ndash27 [CrossRef]30 De la Cruz M Badiano J Gates W Libellus de Medicinalibus Indorum Herbis English The Maya Society London UK 193931 Alcorn JB Huastec Mayan Ethnobotany University Texas Press Austin TX USA 198432 Hernaacutendez-Rodriacuteguez E Loacutepez-Santiago J Uses and Traditional Knowledge of Dendropogonella rufescens (Bryophyta

Cryphaeaceae) in a Zapotec Community of Southeastern Mexico Bot Sci 2021 1 153ndash168 [CrossRef]33 Drobnik J Stebel A Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy

A Review Plants 2021 10 1296 [CrossRef]34 Drobnik J Stebel A Tangled History of the European Uses of Sphagnum Moss and Sphagnol J Ethnopharmacol 2017 209

41ndash49 [CrossRef]

Agronomy 2022 12 1456 17 of 21

35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

37 Valarezo E Tandazo O Galaacuten K Rosales J Beniacutetez Aacute Volatile Metabolites in Liverworts of Ecuador Metabolites 2020 10 92[CrossRef]

38 Saritas Y Sonwa MM Iznaguen H Koumlnig WA Muhle H Mues R Volatile Constituents in Mosses (Musci) Phytochemistry2001 57 443ndash457 [CrossRef]

39 Tosun G Yaylı B Oumlzdemir T Batan N Bozdeveci A Yaylı N Volatiles and Antimicrobial Activity of the Essential Oils ofthe Mosses Pseudoscleropodium purum Eurhynchium striatum and Eurhynchium angustirete Grown in Turkey Rec Nat Prod 2015 9237ndash242

40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

43 Sakurai K Tomiyama K Kawakami Y Yaguchi Y Asakawa Y Characteristic Scent from the Tahitian Liverwort CyathodiumFoetidissimum J Oleo Sci 2018 67 1265ndash1269 [CrossRef]

44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

45 Asakawa Y Joulain D Chemical Constituents of Unidentified Malaysian Liverwort Astrella () Species J Hattori Bot Lab 1995188 183ndash188 [CrossRef]

46 Toyota M Saito T Matsunami J Asakawa Y A Comparative Study on Three Chemo-Types of the Liverwort ConocephalumConicum Using Volatile Constituents Phytochemistry 1997 44 1265ndash1270 [CrossRef]

47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

48 Ludwiczuk A Komala I Pham A Bianchini JP Raharivelomanana P Asakawa Y Volatile Components from SelectedTahitian Liverworts Nat Prod Commun 2009 4 1387ndash1392 [CrossRef]

49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

51 Pannequin A Tintaru A Desjobert JM Costa J Muselli A New Advances in the Volatile Metabolites of Frullania tamarisciFlavour Fragr J 2017 32 409ndash418 [CrossRef]

52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

64 Vats S Alam A Antibacterial Activity of Atrichum undulatum (Hedw) P Beauv against Some Pathogenic Bacteria J Biol Sci2013 13 427ndash431 [CrossRef]

65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

68 Karpinski TM Adamczak A Antibacterial Activity of Ethanolic Extracts of Some Moss Species Herba Pol 2017 63 11ndash17[CrossRef]

69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

77 Nikolajeva V Liepina L Petrina Z Krumina G Grube M Muiznieks I Antibacterial Activity of Extracts from SomeBryophytes Adv Microbiol 2012 02 345ndash353 [CrossRef]

78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

79 Basile A Giordano S Sorbo S Vuotto ML Ielpo MTL Cobianchi RC Antibiotic Effects of Lunularia cruciata (Bryophyta)Extract Pharm Biol 1998 36 25ndash28 [CrossRef]

80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 17: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 17 of 21

35 Krzaczkowski L Wright M Gairin JE Bryophytes a Potent Source of Drugs for Tomorrowrsquos Medicine Med Sci 2008 24947ndash953 [CrossRef]

36 He X Sun Y Zhu RL The Oil Bodies of Liverworts Unique and Important Organelles in Land Plants CRC Crit Rev Plant Sci2013 32 293ndash302 [CrossRef]

37 Valarezo E Tandazo O Galaacuten K Rosales J Beniacutetez Aacute Volatile Metabolites in Liverworts of Ecuador Metabolites 2020 10 92[CrossRef]

38 Saritas Y Sonwa MM Iznaguen H Koumlnig WA Muhle H Mues R Volatile Constituents in Mosses (Musci) Phytochemistry2001 57 443ndash457 [CrossRef]

39 Tosun G Yaylı B Oumlzdemir T Batan N Bozdeveci A Yaylı N Volatiles and Antimicrobial Activity of the Essential Oils ofthe Mosses Pseudoscleropodium purum Eurhynchium striatum and Eurhynchium angustirete Grown in Turkey Rec Nat Prod 2015 9237ndash242

40 Cansu TB Yayli B Oumlzdemir T Batan N Karaoglu SA Yayli N Antimicrobial Activity and Chemical Composition of theEssential Oils of Mosses (Hylocomium splendens (Hedw) Schimp and Leucodon sciuroides (Hedw) Schwaumlgr) Growing in TurkeyTurk J Chem 2013 37 213ndash219 [CrossRef]

41 Ozdemir T Uumlccediluumlncuuml O Cansu T Kahriman N Yaylı N Volatile Constituents in Mosses (Brachythecium albicans (Hedw)Schimp Bryum pallescens Schleich Ex Schwagr and Syntrichia intermedia Brid) Grown in Turkey Asian J Chem 2010 227285ndash7290

42 Xie C Lou H Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Curr Org Chem2008 12 619ndash628 [CrossRef]

43 Sakurai K Tomiyama K Kawakami Y Yaguchi Y Asakawa Y Characteristic Scent from the Tahitian Liverwort CyathodiumFoetidissimum J Oleo Sci 2018 67 1265ndash1269 [CrossRef]

44 Asakawa Y Nii K Higuchi M Identification of Sesquiterpene Lactones in the Bryophyta (Mosses) Takakia Takakia SpeciesAre Closely Related Chemically to the Marchantiophyta (Liverworts) Nat Prod Commun 2015 10 5ndash8 [CrossRef]

45 Asakawa Y Joulain D Chemical Constituents of Unidentified Malaysian Liverwort Astrella () Species J Hattori Bot Lab 1995188 183ndash188 [CrossRef]

46 Toyota M Saito T Matsunami J Asakawa Y A Comparative Study on Three Chemo-Types of the Liverwort ConocephalumConicum Using Volatile Constituents Phytochemistry 1997 44 1265ndash1270 [CrossRef]

47 Ghani NA Ludwiczuk A Ismail NH Asakawa Y Volatile Components of the Stressed Liverwort Conocephalum ConicumNat Prod Commun 2016 11 103ndash104 [CrossRef]

48 Ludwiczuk A Komala I Pham A Bianchini JP Raharivelomanana P Asakawa Y Volatile Components from SelectedTahitian Liverworts Nat Prod Commun 2009 4 1387ndash1392 [CrossRef]

49 Allen NS Santana AI Gomez N Chung C Gupta MP Identification of Volatile Compounds from Three Species ofCyathodium (Marchantiophyta Cyathodiaceae) and Leiosporoceros dussii (Anthocerotophyta Leiosporocerotaceae) from Panamaand C Foetidissimum from Costa Rica Bol Soc Argent Bot 2017 52 357ndash370 [CrossRef]

50 Tori M Sono M Asakawa Y Absolute Configuration and Synthesis of the Liverwort Sesquiterpene Alcohol TamariscolJ Chem Soc Perkin Trans 1990 1 2849ndash2850 [CrossRef]

51 Pannequin A Tintaru A Desjobert JM Costa J Muselli A New Advances in the Volatile Metabolites of Frullania tamarisciFlavour Fragr J 2017 32 409ndash418 [CrossRef]

52 Buchanan MS Natural Products from the Hepaticae University of Glasgow Glasgow Scotland 199453 Toyota M Koyama H Asakawa Y Volatile Components of the Liverworts Archilejeunea Olivacea Cheilolejeunea imbricata and

Leptolejeunea elliptica Phytochemistry 1997 44 1261ndash1264 [CrossRef]54 Sakurai K Tomiyama K Yaguchi Y Asakawa Y Characteristic Odor of the Japanese Liverwort (Leptolejeunea elliptica) J Oleo

Sci 2020 69 767ndash770 [CrossRef] [PubMed]55 Toyota M Asakawa Y Frahm JT Homomono- and Sesquiterpenoids from the Liverwort Lophocolea heterophylla Phytochemistry

1990 29 2334ndash2337 [CrossRef]56 Huneck S Connolly JD Freer AA Rycroft DS Grimaldone a Tricyclic Sesquiterpenoid from Mannia fragrans Crystal

Structure Analysis Phytochemistry 1988 27 1405ndash1407 [CrossRef]57 Choi SS Bakalin VA Park SJ Sim SH Hyun CW Unrecorded Liverwort Species from Korean Flora III New Data on the

Distribution of Mannia opiz (Marchantiophyta) Korean J Plant Taxon 2020 50 227ndash231 [CrossRef]58 Heinrichs J Groth H Gradstein SR Rycroft DS Cole WJ Anton H Plagiochila rutilans (Hepaticae) A Poorly Known

Species from Tropical America Bryologist 2001 104 350ndash361 [CrossRef]59 Rycroft DS Cole WJ Hydroquinone Derivatives and Monoterpenoids from the Neotropical Liverwort Plagiochila rutilans

Phytochemistry 2001 57 479ndash488 [CrossRef]60 Allen NS Becker H Gupta MP Occurrence of (-)-Geosmin and Other Terpenoids in an Axenic Culture of the Liverwort

Symphyogyna brongniartii Z Fur Naturforsch Sect C J Biosci 1991 46 183ndash188 [CrossRef]61 Bukvicki DR Tyagi AK Gottardi DG Veljic MM Jankovic SM Guerzoni ME Marin PD Assessment of the Chemical

Composition and in Vitro Antimicrobial Potential of Extracts of the Liverwort Scapania Aspera Nat Prod Commun 2013 81313ndash1316 [CrossRef] [PubMed]

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

64 Vats S Alam A Antibacterial Activity of Atrichum undulatum (Hedw) P Beauv against Some Pathogenic Bacteria J Biol Sci2013 13 427ndash431 [CrossRef]

65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

68 Karpinski TM Adamczak A Antibacterial Activity of Ethanolic Extracts of Some Moss Species Herba Pol 2017 63 11ndash17[CrossRef]

69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

77 Nikolajeva V Liepina L Petrina Z Krumina G Grube M Muiznieks I Antibacterial Activity of Extracts from SomeBryophytes Adv Microbiol 2012 02 345ndash353 [CrossRef]

78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

79 Basile A Giordano S Sorbo S Vuotto ML Ielpo MTL Cobianchi RC Antibiotic Effects of Lunularia cruciata (Bryophyta)Extract Pharm Biol 1998 36 25ndash28 [CrossRef]

80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 18: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 18 of 21

62 Singh M Singh S Nath V Sahu V Singh Rawat AK Antibacterial Activity of Some Bryophytes Used Traditionally for theTreatment of Burn Infections Pharm Biol 2011 49 526ndash530 [CrossRef] [PubMed]

63 Saxena K Yadav U In Vitro Assessment of Antimicrobial Activity of Aqueous and Alcoholic Extracts of Moss Atrichumundulatum (Hedw) P Beauv Physiol Mol Biol Plants 2018 24 1203ndash1208 [CrossRef] [PubMed]

64 Vats S Alam A Antibacterial Activity of Atrichum undulatum (Hedw) P Beauv against Some Pathogenic Bacteria J Biol Sci2013 13 427ndash431 [CrossRef]

65 Sabovljevic A Sokovic M Glamoclija J Ciric A Vujicic M Pejin B Sabovljevic M Bio-Activities of Extracts from SomeAxenically Farmed and Naturally Grown Bryophytes J Med Plants Res 2011 5 565ndash571

66 Sabovljevic A Sokovic M Glamocija J Ciric A Vujicic M Pejin B Sobvljevic M Comparison of Bio-Activities of in Situand in Vitro Grown Selected Bryophyte Species Afr J Microbiol Res 2010 4 808ndash812

67 Sabovljevic A Sokovic M Sabovljevic M Grubisic D Antimicrobial Activity of Bryum argenteum Fitoterapia 2006 77 144ndash145[CrossRef]

68 Karpinski TM Adamczak A Antibacterial Activity of Ethanolic Extracts of Some Moss Species Herba Pol 2017 63 11ndash17[CrossRef]

69 Veljic M Duric A Sokovic M Ciric A Glamoclija J Marin PD Antimicrobial Activity of Methanol Extracts of Fontinalisantipyretica Hypnum cupressiforme and Ctenidium molluscum Arch Biol Sci 2009 61 225ndash229 [CrossRef]

70 Uumlccediluumlncuuml O Cansu TB Oumlzdemlr T Alpay Karaoglu S Yayli N Chemical Composition and Antimicrobial Activity of theEssential Oils of Mosses (Tortula muralis Hedw Homalothecium lutescens (Hedw) H Rob Hypnum cupressiforme Hedw and Pohlianutans (Hedw) Lindb) from Turkey Turk J Chem 2010 34 825ndash834 [CrossRef]

71 Vollaacuter M Gyovai A Szucs P Zupkoacute I Marschall M Csupor-Lffler B Beacuterdi P Vecsernyeacutes A Csorba ALiktor-Busa E et al Antiproliferative and Antimicrobial Activities of Selected Bryophytes Molecules 2018 23 1520 [CrossRef]

72 Yucel TB Chemical Composition and Antimicrobial and Antioxidant Activities of Essential Oils of Polytrichum commune (Hedw)and Antitrichia curtipendula (Hedw) Brid Grown in Turkey Int J Second Metab 2021 8 272 [CrossRef]

73 Klavina L Springe G Nikolajeva V Martsinkevich I Nakurte I Dzabijeva D Steinberga I Chemical Composition AnalysisAntimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry) Molecules 2015 20 17221ndash17243[CrossRef] [PubMed]

74 Savaroglu F Ilhan S Filik-Iscen C An Evaluation of the Antimicrobial Activity of Some Turkish Mosses J Med Plants Res2011 5 3286ndash3292

75 Scher JM Speakman JB Zapp J Becker H Bioactivity Guided Isolation of Antifungal Compounds from the LiverwortBazzania trilobata (L) SF Gray Phytochemistry 2004 65 2583ndash2588 [CrossRef] [PubMed]

76 Vujicic M Dimkic I Sabovljevic A Stankovic S Sabovljevic M Effects of Selected Bryophyte Species Extracts on Microorgan-isms Acta Biol Plant Agriensis 2017 5 63 [CrossRef]

77 Nikolajeva V Liepina L Petrina Z Krumina G Grube M Muiznieks I Antibacterial Activity of Extracts from SomeBryophytes Adv Microbiol 2012 02 345ndash353 [CrossRef]

78 Bukvicki D Gottardi D Vannini L Dzamic A Ciric A Marin PD Veljic M Chemical Composition and AntimicrobialAssessment of Liverwort Lophozia Ventricosa Extracts Rev Bras Bot 2015 38 25ndash30 [CrossRef]

79 Basile A Giordano S Sorbo S Vuotto ML Ielpo MTL Cobianchi RC Antibiotic Effects of Lunularia cruciata (Bryophyta)Extract Pharm Biol 1998 36 25ndash28 [CrossRef]

80 Dhondiyal PB Pande N Bargali K Antibiotic Potential of Lunularia cruciata (L) Dum Ex Lindb (Bryophyta) of KumaonHimalaya Afr J Microbiol Res 2013 7 4350ndash4354

81 Mewari N Kumar P Antimicrobial Activity of Extracts of Marchantia Polymorpha Pharm Biol 2008 46 819ndash822 [CrossRef]82 Gahtori D Chaturvedi P Antifungal and Antibacterial Potential of Methanol and Chloroform Extracts of Marchantia polymorpha

L Arch Phytopathol Plant Prot 2011 44 726ndash731 [CrossRef]83 Kumar Tyagi A Bukvicki D Gottardi D Veljic M Guerzoni ME Malik A Marin PD Antimicrobial Potential and

Chemical Characterization of Serbian Liverwort (Porella arboris-vitae) SEM and TEM Observations Evid Based ComplementAltern Med 2013 2013 1ndash7 [CrossRef] [PubMed]

84 Sharma C Sharma A Katoch M Comparative Evaluation of Antimicrobial Activity of Methanolic Extract and PhenolicCompounds of a Liverwort Reboulia hemispherica Arch Bryol 2013 193 1ndash6

85 Alam A Charan Sharma S Sharma V In Vitro Antifungal Efficacies of Aqueous Extract of Targionia hypophylla L againstGrowth Of Some Pathogenic Fungi Int J Ayurvedic Herb Med 2012 2 229ndash233

86 Sawant Ulka J Karadge BA Antimicrobial Activity of Some Bryophytes (Liverworts and a Hornwort) from Kolhapur DistrictPharmacogn J 2010 2 25ndash28 [CrossRef]

87 Lu ZQ Fan PH Ji M Lou HX Terpenoids and Bisbibenzyls from Chinese Liverworts Conocephalum conicum and Dumortierahirsuta J Asian Nat Prod Res 2006 8 187ndash192 [CrossRef]

88 Asakawa Y Highlights in Phytochemistry of Hepaticaebiologically Active Terpenoids and Aromatic Compounds Pure ApplChem 1994 66 2193ndash2196 [CrossRef]

89 Zinsmeister HD Becker H Eicher T Bryophytes a Source of Biologically Active Naturally Occurring Material Angew ChemInt Ed Engl 1991 30 130ndash147 [CrossRef]

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 19: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 19 of 21

90 Perry NB Foster LM SesquiterpeneQuinol from a New Zealand Liverwort Riccardia Crassa J Nat Prod 1995 58 1131ndash1135[CrossRef]

91 Horn A Pascal A Loncarevic I Volpatto Marques R Lu Y Miguel S Bourgaud F Thorsteinsdoacutettir M Cronberg NBecker JD et al Natural Products from Bryophytes From Basic Biology to Biotechnological Applications CRC Crit Rev PlantSci 2021 40 191ndash217 [CrossRef]

92 Nandy S Dey A Bibenzyls and Bisbybenzyls of Bryophytic Origin as Promising Source of Novel Therapeutics PharmacologySynthesis and Structure-Activity DARU J Pharm Sci 2020 28 701ndash734 [CrossRef] [PubMed]

93 Dey A Mukherjee A Therapeutic Potential of Bryophytes and Derived Compounds against Cancer J Acute Dis 2015 4236ndash248 [CrossRef]

94 Qu J Xie C Guo H Yu W Lou H Antifungal Dibenzofuran Bis(Bibenzyl)s from the Liverwort Asterella AngustaPhytochemistry 2007 68 1767ndash1774 [CrossRef]

95 Asakawa Y Polyphenols in Bryophytes Structures Biological Activities and Bio- and Total Syntheses Recent Adv Polyphen Res2016 5 36ndash66 [CrossRef]

96 Niu C Qu JB Lou HX Antifungal Bis(Bibenzyls) from the Chinese Liverwort Marchantia polymorpha L Chem Biodivers 20063 34ndash40 [CrossRef]

97 Xie CF Qu JB Wu XZ Liu N Ji M Lou HX Antifungal Macrocyclic Bis(Bibenzyls) from the Chinese LiverwortPtagiochasm intermedlum L Nat Prod Res 2010 24 515ndash520 [CrossRef]

98 Govindachari TR Viswanathan N Pai BR Savitri TS Chemical Constituents of RBr Elsevier Amsterdam The Netherlands1964 Volume 5

99 Guo YX Lin ZM Wang MJ Dong YW Niu HM Young CYF Lou HX Yuan HQ Jungermannenone A and B InduceROS-and Cell Cycle-Dependent Apoptosis in Prostate Cancer Cells in Vitro Acta Pharmacol Sin 2016 37 814ndash824 [CrossRef]

100 Xu AH Hu ZM Qu JB Liu SM Syed AKA Yuan HQ Lou HX Cyclic Bisbibenzyls Induce Growth Arrest andApoptosis of Human Prostate Cancer PC3 Cells Acta Pharmacol Sin 2010 31 609ndash615 [CrossRef]

101 Gaweł-Beben K Osika P Asakawa Y Antosiewicz B Głowniak K Ludwiczuk A Evaluation of Anti-Melanoma andTyrosinase Inhibitory Properties of Marchantin A a Natural Macrocyclic Bisbibenzyl Isolated from Marchantia Species PhytochemLett 2019 31 192ndash195 [CrossRef]

102 Scher JM Burgess EJ Lorimer SD Perry NB A Cytotoxic Sesquiterpene and Unprecedented Sesquiterpene-BisbibenzylCompounds from the Liverwort Schistochila Glaucescens Tetrahedron 2002 58 7875ndash7882 [CrossRef]

103 Zheng GQ Ho DK Elder PJ Stephens RE Cottrell CE Cassady JM Ohioensins and Pallidisetins Novel CytotoxicAgents from the Moss Polytrichum pallidisetum J Nat Prod 1994 57 32ndash41 [CrossRef] [PubMed]

104 Novakovic M Bukvicki D Andjelkovic B Ilic-Tomic T Veljic M Tesevic V Asakawa Y Cytotoxic Activity of Riccardinand Perrottetin Derivatives from the Liverwort Lunularia cruciata J Nat Prod 2019 82 694ndash701 [CrossRef] [PubMed]

105 Novakovic M Ludwiczuk A Bukvicki D Asakawa Y Phytochemicals from Bryophytes Structures and Biological ActivityJ Serb Chem Soc 2021 86 1139ndash1175 [CrossRef]

106 Yue XF Han JX Shen ZM Yang WY Lu LJ Li BJ Wang C Xu XK Cytotoxic Activity of Trewiasine in 4 HumanCancer Cell Lines and 5 Murine Tumors Acta Pharmacol Sin 1992 13 252ndash255

107 Toyota M Kinugawa T Asakawa Y Bibenzyl Cannabinoid and Bisbibenzyl Derivative from the liverwort Radula perrottetiiPhytochemistry 1994 37 859ndash862 [CrossRef]

108 Asakawa Y Nagashima F Ludwiczuk A Distribution of Bibenzyls Prenyl Bibenzyls Bis-Bibenzyls and Terpenoids in theLiverwort Genus Radula J Nat Prod 2020 83 756ndash769 [CrossRef]

109 Toyota M Shimamura T Ishii H Renner M Braggins J Asakawa Y New Bibenzyl Cannabinoid from the New ZealandLiverwort Radula marginata Chem Pharm Bull 2002 50 1390ndash1392 [CrossRef]

110 Cullmann F Becker H Prenylated Bibenzyls from the Liverwort Radula Laxiramea Z Fur Naturforsch Sect C J Biosci 1999 54147ndash150 [CrossRef]

111 Chicca A Schafroth MA Reynoso-Moreno I Erni R Petrucci V Carreira EM Gertsch J Uncovering the Psychoactivity ofa Cannabinoid from Liverworts Associated with a Legal High Sci Adv 2018 4 1ndash11 [CrossRef]

112 Becquerel P Germination Des Spores drsquoAtrichum Undulatum et drsquoHypnum Velutinum Nutrition et Developpement de LeursProtonema Dans Des Milieux Sterilises Rev Gen Bot 1906 18 49ndash67

113 Servettaz C Recherches Experimentales Sur Le Developpement et La Nutrition Des Mousses En Milieux Sterilises Ann Sci NatBot Biol Veg 1913 17 111ndash223

114 Laibach F Das Taubwerden von Bastardsamen Und Die Kuumlnstliche Aufzucht Fruumlh Absterbender Bastardembryonen Z Fuumlr Bot1925 17 417ndash459

115 Hohe A Reski R From Axenic Spore Germination to Molecular Farming One Century of Bryophyte in Vitro Culture Plant CellRep 2005 23 513ndash521 [CrossRef]

116 Becker H Moose Und Ihre Biologisch Aktiven Naturstoffe Z Fuumlr Phyther 2001 22 152ndash158117 Sabovljevic A Sabovljevic M Jockovic N In Vitro Culture and Secondary Metabolite Isolation in Bryophytes Methods Mol

Biol 2009 547 117ndash128 [CrossRef]118 Peters K Gorzolka K Bruelheide H Neumann S Seasonal Variation of Secondary Metabolites in Nine Different Bryophytes

Ecol Evol 2018 8 9105ndash9117 [CrossRef]

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 20: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 20 of 21

119 Guo L Wu JZ Han T Cao T Rahman K Qin LP Chemical Composition Antifungal and Antitumor Properties of EtherExtracts of Scapania verrucosa Heeg and Its Endophytic Fungus Chaetomium fusiforme Molecules 2008 13 2114ndash2125 [CrossRef]

120 Suwanborirux K Chang CJ Spjut RW Cassady JM Ansamitocin P-3 a Maytansinoid from Claopodium crispifolium andAnomodon attenuatus or Associated Actinomycetes Experientia 1990 46 117ndash120 [CrossRef]

121 Stelmasiewicz M Swiatek Ł Ludwiczuk A Phytochemical Profile and Anticancer Potential of Endophytic Microorganismsfrom Liverwort Species Marchantia polymorpha L Molecules 2022 27 153 [CrossRef]

122 Anderson M Lambrinos J Schroll E The Potential Value of Mosses for Stormwater Management in Urban EnvironmentsUrban Ecosyst 2010 13 319ndash332 [CrossRef]

123 Glime J The Fauna A Place to Call Home Bryophyt Ecol 2017 2 1ndash15124 Sterlyagova I Shabalina J Algae in Sphagnum Epiphyton from the Mires of the Subpolar Urals Bot Lith 2017 23 3ndash16

[CrossRef]125 Adams DG Duggan PS Cyanobacteria-Bryophyte Symbioses J Exp Bot 2008 59 1047ndash1058 [CrossRef] [PubMed]126 Holland-Moritz H Stuart JEM Lewis LR Miller SN Mack MC Ponciano JM McDaniel SF Fierer N The Bacterial

Communities of Alaskan Mosses and Their Contributions to N2-Fixation Microbiome 2021 9 1ndash14 [CrossRef] [PubMed]127 Jean M Holland-Moritz H Melvin AM Johnstone JF Mack MC Experimental Assessment of Tree Canopy and Leaf Litter

Controls on the Microbiome and Nitrogen Fixation Rates of Two Boreal Mosses New Phytol 2020 227 1335ndash1349 [CrossRef]128 Stewart KJ Lamb EG Coxson DS Siciliano SD Bryophyte-Cyanobacterial Associations as a Key Factor in N2-Fixation

across the Canadian Arctic Plant Soil 2011 344 335ndash346 [CrossRef]129 Arroacuteniz-Crespo M Peacuterez-Ortega S De Los Riacuteos A Green TGA Ochoa-Hueso R Erratum Bryophyte-Cyanobacteria

Associations during Primary Succession in Recently Deglaciated Areas of Tierra Del Fuego (Chile) (PLoS ONE (2014) 99(E108759)) PLoS ONE 2014 9 96081 [CrossRef]

130 Orlinski R Multipoint Moss Passive Samplers Assessment of Urban Airborne Polycyclic Aromatic Hydrocarbons ConcentrationsProfile and Distribution along Warsaw Main Streets Chemosphere 2002 48 181ndash186 [CrossRef]

131 Dolegowska S Migaszewski ZM PAH Concentrations in the Moss Species Hylocomium splendens (Hedw) BSG and Pleuroziumschreberi (Brid) Mitt from the Kielce Area (South-Central Poland) Ecotoxicol Environ Saf 2011 74 1636ndash1644 [CrossRef]

132 Salemaa M Derome J Helmisaari HS Nieminen T Vanha-Majamaa I Element Accumulation in Boreal Bryophytes Lichensand Vascular Plants Exposed to Heavy Metal and Sulfur Deposition in Finland Sci Total Environ 2004 324 141ndash160 [CrossRef][PubMed]

133 Gerdol R Bragazza L Marchesini R Medici A Pedrini P Benedetti S Bovolenta A Coppi S Use of Moss (Tortula muralisHedw) for Monitoring Organic and Inorganic Air Pollution in Urban and Rural Sites in Northern Italy Atmos Environ 2002 364069ndash4075 [CrossRef]

134 Giordano S Adamo P Spagnuolo V Tretiach M Bargagli R Accumulation of Airborne Trace Elements in Mosses Lichens andSynthetic Materials Exposed at Urban Monitoring Stations Towards a Harmonisation of the Moss-Bag Technique Chemosphere2013 90 292ndash299 [CrossRef] [PubMed]

135 Cianciullo P Maresca V Sorbo S Basile A Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds inBryophytes Appl Sci 2022 12 160 [CrossRef]

136 Tellez-Rocha N Moncada B Pombo-Ospina LM Rodriguez-Aguirre OE Actividad Antioxidante De Los Musgos BreuteliaSubdisticha Leptodontium Viticulosoides y Pylaisia Falcata Cienc En Desarro 2021 12 1ndash20 [CrossRef]

137 Gahtori D Chaturvedi P Bryophytes A Potential Source of Antioxidants In Bryophytes IntechOpen London UK 2020pp 1ndash12 [CrossRef]

138 Marques RV Sestito SE Bourgaud F Miguel S Cailotto F Reboul P Jouzeau J-Y Rahuel-Clermont S Boschi-Muller SSimonsen HT et al Anti-Inflammatory Activity of Bryophytes Extracts in LPS-Stimulated RAW2647 Murine macrophagesMolecules 2022 27 1940 [CrossRef]

139 Li S Niu H Qiao Y Zhu R Sun Y Ren Z Yuan H Gao Y Li Y Chen W et al Terpenoids Isolated from ChineseLiverworts Lepidozia Reptans and Their Anti-Inflammatory Activity Bioorganic Med Chem 2018 26 2392ndash2400 [CrossRef]

140 Li Y Zhu R Zhang J Wu X Shen T Zhou J Qiao Y Gao Y Lou H Clerodane Diterpenoids from the Chinese LiverwortJamesoniella Autumnalis and Their Anti-Inflammatory Activity Phytochemistry 2018 154 85ndash93 [CrossRef]

141 Asakawa Y Ludwiczuk A Hashimoto T Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi J Pre-ClinClin Res 2014 7 73ndash85 [CrossRef]

142 Ludwiczuk A Asakawa Y Terpenoids and Aromatic Compounds from Bryophytes and Their Central Nervous System ActivityCurr Org Chem 2020 24 113ndash128 [CrossRef]

143 Lunic TM Mandic MR Oalde Pavlovic MM Sabovljevic AD Sabovljevic MS Božic Nedeljkovic B Božic B TheInfluence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum CupressiformeExtracts In Vitro and in Silico Study Plants 2022 11 123 [CrossRef] [PubMed]

144 Asakawa Y Ludwiczuk A Chemical Constituents of Bryophytes Structures and Biological Activity J Nat Prod 2018 81641ndash660 [CrossRef] [PubMed]

145 Abay G Karakoccedil OumlC Tuumlfekccedili AR Koldas S Demirtas I Insecticidal Activity of Hypnum cupressiforme (Bryophyta) againstSitophilus granarius (Coleoptera Curculionidae) J Stored Prod Res 2012 51 6ndash10 [CrossRef]

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References
Page 21: Modern Use of Bryophytes as a Source of Secondary ... - MDPI

Agronomy 2022 12 1456 21 of 21

146 Ramiacuterez M Kamiyab N Popich S Asakawa Y Bardoacuten A Constituents of the Argentine Liverwort Plagiochila diversifolia andTheir Insecticidal Activities Chem Biodivers 2017 14 1ndash17 [CrossRef] [PubMed]

147 Asakawa Y Ludwiczuk A Bryophytes Liverworts Mosses and Hornworts Extraction and Isolation Procedures In Methods inMolecular Biology Springer BerlinHeidelberg Germany 2013 Volume 1055 pp 1ndash20 ISBN 9781627035767

148 Krishnan R Murugan K Axenic Culture of Bryophytes A Case Study of Liverwort Marchantia Linearis Lehm amp LindenbIndian J Biotechnol 2014 13 131ndash135

149 Beike AK Horst NA Rensing SA Axenic Bryophyte in Vitro Cultivation J Endocytobiosis Cell Res 2010 20 102ndash108150 Duckett JG Burch J Fletcher PW Matcham HW Read DJ Russell AJ Pressel S In Vitro Cultivation of Bryophytes A

Review of Practicalities Problems Progress and Promise J Bryol 2004 26 3ndash20

  • Introduction
  • Ethnopharmacology
  • Secondary Metabolites
    • Volatile Compounds
    • Antimicrobial Compounds and Extracts
    • Cytotoxic Compounds
    • Other Compounds
      • Bryophytes in Tissue Cultures
      • Conclusions
      • References

Secondary Footprints 2021-2022

Secondary Footprints 2021-2022

Turnover of recently assimilated carbon in arctic bryophytes

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MICROPROPAGATION AND SECONDARY METABOLITE ...

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RNA Secondary Structures

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Untitled - Unity Secondary School

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AEG - Source - Mercenaries.pdf

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Download Source-

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Seeking the source

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Newsletter - Bellarine Secondary College

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SECONDARY SCHOOL EDUCATION - MOE

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Production of microbial secondary metabolites: Regulation by the carbon source

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Bryophytes in black alder swamps in south Sweden - Lindbergia

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publication.pdf - Teach Secondary

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Source link - Typeset

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Goa Board Of Secondary and Higher Secondary Education

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Retention of Inorganic Nitrogen by Epiphytic Bryophytes in a Tropical Montane Forest1

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International Secondary Catalogue 2019

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Bryo-Activities: A Review on How Bryophytes Are ... - MDPI

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Endemic genera of bryophytes of North America (north of Mexico

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SOURCE Bulletin - IW:LEARN

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