Liu-etal Seaweeds JEP142-2012

Journal of Ethnopharmacology 142 (2012) 591–619

Contents lists available at SciVerse ScienceDirect

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Review

Towards a better understanding of medicinal uses of the brown seaweedSargassum in Traditional Chinese Medicine: A phytochemical andpharmacological review

Lei Liu a,n, Michael Heinrich a,b, Stephen Myers a, Symon A. Dworjanyn c

a Southern Cross Plant Science, Southern Cross University, PO Box 157, Lismore, NSW 2480, Australiab Centre for Pharmacognosy and Phytotherapy, UCL School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UKc National Marine Science Centre, Southern Cross University, Coffs Harbour, NSW 2450, Australia

a r t i c l e i n f o

Article history:

Received 29 February 2012

Received in revised form

18 April 2012

Accepted 25 May 2012Available online 6 June 2012

Keywords:

Sargassum

Traditional Chinese Medicine (TCM)

Thyroid

Meroterpenoids

Phlorotanin

Fucoidan

Immunomodulator

Hashimoto’s thyroiditis

41/$ - see front matter & 2012 Elsevier Irelan

x.doi.org/10.1016/j.jep.2012.05.046

viations: AAPT, activated partial thromboplas

oride; COX, cyclooxygenase; CPR, C-reactive

thyl acetate; ET, endothelin; HCMV, human

inase; GSH, glutathione; HAV, Hepatitis A Vi

ydrogen peroxide; HPLC, high performance li

ymphotropic Virus Type 1; IgE, Immunoglobu

roxidation; MeOH, methanol; MIT, monoiodot

uclear magnetic resonance; NGF, nerve grow

d receptors; PT, prothrombin time; ROS, reac

aditional Chinese medicine; Tg, thyroglobulin

y; TT, thrombin time; UVB, ultraviolet B; VLD

esponding author. Tel.: þ61 2 66223211; fax

ail addresses: [email protected], [email protected]

[email protected] (S.A. Dworjanyn).

a b s t r a c t

Ethnopharmacological relevance: For nearly 2000 years Sargassum spp., a brown seaweed, has been used in

Traditional Chinese Medicine (TCM) to treat a variety of diseases including thyroid disease (e.g. goitre).

Aims of the review: To assess the scientific evidence for therapeutic claims made for Sargassum spp. in TCM

and to identify future research needs.

Background and methods: A systematic search for the use of Sargassum in classical TCM books was conducted

and linked to a search for modern phytochemical and pharmacological data on Sargassum spp. retrieved from

PubMed, Web of Knowledge, SciFinder Scholar and CNKI (in Chinese).

Results and discussion: The therapeutic effects of Sargassum spp. are scientifically plausible and may be

explained partially by key in vivo and in vitro pharmacological activities of Sargassum, such as anticancer, anti-

inflammatory, antibacterial and antiviral activities. Although the mechanism of actions is still not clear, the

pharmacological activities could be mainly attributed to the major biologically active metabolites, mer-

oterpenoids, phlorotanins and fucoidans. The contribution of iodine in Sargassum for treating thyroid related

diseases seem to have been over estimated.

Conclusions: The bioactive compounds in Sargassum spp. appear to play a role as immunomodulators and

could be useful in the treatment of thyroid related diseases such as Hashimoto’s thyroiditis. Further research

is required to determine both the preventative and therapeutic role of Sargassum spp. in thyroid health.

& 2012 Elsevier Ireland Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 592

2. Botany and taxonomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 592

3. Traditional uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 594

4. Phytochemistry and pharmacological activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 594

4.1. Meroterpenoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595

4.2. Phlorotanins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595

d Ltd. All rights reserved.

tin time; ABTS, 2,20-azinobis-3-ethylbenzo thizoline-6-sulphonate; BT, bleeding time; BuOH, butanol; CCl4, carbon

protein; CT, coagulation time; DCM, dichloromethane; DIT, diiodotyrosine; DPPH, 1,1-diphenyl-2-picrylhydrazyl;

cytomegalovirus; GC, gas chromatography; GOT, glutamic oxaloacetic transminase; GPT, glutamic pyruvic

rus; HCMV, human cytomegalovirus; HDL, high-density lipoprotein; HIV-1, Human Immunodeficiency Virus Type 1;

quid chromatography; HSV-1, Herpes Simplex Virus Type 1; HSV-2, Herpes Simplex Virus Type 2; HTLV-1, Human

lin E; IL, interleukin; INF-b, interferon b; iNOS, inducible nitric oxide synthase; LDL, Low-density lipoprotein; LPO,

yrosine; M/G, mannuronic acid/guluronic acid; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells;

th factor; NO, nitric oxide; PARP, poly ADP-ribose polymerase; PG, prostaglandin; PPAR, peroxisome proliferator-

tive oxygen species; Seq., Sequential (extraction); SOD, superoxide dismutase; T3, triiodothyronine; T4, thyroxine;

; TgAb, thyroglobulin antibody; TNF-a, tumour necrosis factor-alpha; TPO, thyroperoxidase; TPOAb, thyroperoxidase

L, very low-density lipoprotein

: þ61 2 66223459.

u.au (L. Liu), [email protected] (M. Heinrich), [email protected] (S. Myers),

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dx.doi.org/10.1016/j.jep.2012.05.046

dx.doi.org/10.1016/j.jep.2012.05.046

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mailto:[email protected]





dx.doi.org/10.1016/j.jep.2012.05.046

L. Liu et al. / Journal of Ethnopharmacology 142 (2012) 591–619592

4.3. Polysaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595

4.3.1. Fucoidans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595

4.3.2. Alginates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 599

4.4. Other compounds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 603

4.4.1. Phytosterols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 603

4.4.2. Bisnorditerpenens and farnesylacetones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 603

4.4.3. Polyunsaturated fatty acids and glycolipids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 604

4.4.4. Arsenosugars . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605

4.4.5. Iodoamino acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605

4.4.6. Dipeptides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605

4.4.7. Flavonoids and coumarins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605

4.4.8. Miscellaneous compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605

5. Pharmacological properties of Sargassum extracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605

5.1. Anti-inflammatory activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605

5.2. Anti-allergic activity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609

5.3. Antimicrobial, antiviral and antiplasmodial activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609

5.4. Anticancer activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609

5.5. Liver and bone protective activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 611

5.6. Other pharmacological activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 611

6. Safety, traditional and modern issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 611

7. Future research for Sargassum with focus on thyroid health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 611

8. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615

Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615

1. Introduction

Sargassum, a genus of brown seaweed (Phaeophyceae) in theSargassaceae family, contains approximately 400 species (Mattioand Payri, 2011). Sargassum is found throughout all oceans andconsumed as food and medicines in many cultures. Bioactivecompounds (currently about 200), such as meroterpenoids, phlor-otanins, fucoidans, sterols and glycolipids, have been identifiedfrom this genus. A wide range of pharmacological properties of theSargassum spp. extracts or isolated pure components have beenrecognised. These include anticancer, antibacterial, antifungal, anti-viral, anti-inflammatory, anticoagulant, antioxidant, hypoglycaemic,hypolipidemic, antimelanogenic, anti-bone loss, hepatoprotectiveand neuroprotective activities; which suggests that Sargassum is arich source of health maintaining and promoting agents. However,the numerous species, complex chemistry and various pharmaco-logical properties of Sargassum necessitate a systematic and criticalassessment of the future directions of research and application.

The English common names for Sargassum spp. (in the follow-ing called ‘Sargassum’) is gulfweed or sea holly. In Asia, where themajority of ethnopharmacological knowledge is found, Sargassum

species have numerous common names like ‘‘Hai Zao’’ ( ) or‘‘Hai Qian’’ ( ) in Chinese, ‘‘Hondawara’’ ( ) in Japanese,and ‘‘Mojaban’’ ( ) in Korean. Traditional Chinese Medicine(TCM) contains valuable information for the uses of Sargassum,which have been recorded in ancient manuscripts and sum-marised in recently published books such as Chinese Pharmaco-poeias, Compendium of Materia Medica (‘‘Ben Cao Gang Mu’’,

), ‘‘Zhong Hua Ben Cao’’ ( ), and ‘‘Zhong Hua HaiYang Ben Cao’’ ( ).

The biomedical literatures on modern phytochemical andpharmacological studies of Sargassum have increased dramati-cally (30 articles in the 1980s, 78 articles in the 1990s and 386articles in 2000–2011 cited in PubMed, Web of Knowledge andSciFinder Scholar). Search of the China Knowledge ResourceIntegrated Database (CNKI, http://eng.cnki.net/ last accessed at29/02/2012), a Chinese publication database, suggested therehave been 136 peer-reviewed reports (in Chinese) on the chem-istry and medicinal property of Sargassum since 1979. Althoughmost of these studies were initiated according to traditionalknowledge of Sargassum, the connections between the traditional

uses and modern scientific studies have not been systematicallyexamined. The aim of this review was to assess the scientificevidence for the therapeutical claims for Sargassum used in TCMand provide the opportunity for future research, for a moreevidence-based approach to the species use and potentially tothe development of novel supplements or herbal medicines(Uzuner et al., 2012).

2. Botany and taxonomy

Sargassum was first described nearly 200 years ago by Agardh(1820). It is from the order Fucales or rockweeds and in temperateregions it can be common but is less conspicuous than the kelps. Intropical seas it is the dominant most conspicuous upright macro-algae and plays a major role in structuring ecosystems. Sargassum

often detaches from reefs and forms vast pelagic mats and somespecies have a solely pelagic life cycle. It is these large floatingmasses of Sargassum that gives the Sargasso Sea its name. Thegenus, with complex and variable morphology, has been estimatedto be the most species rich genus of the marine macrophytes with�400 species being identified to date (Mattio and Payri, 2011).

Sargassum is characterised by holdfast that attaches to thesubstrate, a short stipe that differentiates into numerous primarybranches that mostly have many leaf like laterals. Sphericalvesicles that aid floatation are often present and reproductivestructures are contained in specialised laterals called receptacles.The shape of the leaf like thallus, vesicles and receptacles arehighly diversified. Even within the same species, Sargassum

morphology significantly varies under different environmentalconditions and at different seasons (Kilar et al., 1992). Due tothese variations, it is often a difficult task to identify Sargassum

species especially from the diverse tropical flora.Only 78 Sargassum species (less than 20% of all identified

Sargassum species) have been investigated for their phytochem-ical and pharmacological properties. The majority of studiesconcentrated on 18 species, of which 11 have been frequentlyused in TCM (Table 1). When used in TCM, Sargassum seaweedsare dried for easy storage and transportation. Once dried it ismore difficult to distinguish the specific Sargassum species. Littleresearch has been carried out on the comparative chemistry,

http://eng.cnki.net/

Table 1Sargassum used in Traditional Chinese Medicine (TCM).

Sargassum used in TCM Species Chinese name for the species Traditional use Reference

‘‘Hai Zao’’ S. pallidum (Turner) C. Agardha ‘‘Hai Hao Zi’’ Used to treat (a) ‘‘Zhong Hua Ben Cao’’,

(b) ‘‘Zhong Guo Yao Yong Zhi Wu Tu

Jian’’,

(c) ‘‘Qing Dao Zhong Yao Shou Ce’’,

(d) ‘‘Zhong Guo Yao Yong Bao Zi Zhi

Wu’’,

(e) ‘‘Fu Jian Yao Wu Zhi’’,

(f) ‘‘Xian Dai Shi Yong Zhong Yao’’,

(a) Goitre, scrofula, swelling and

pain of testes, oedema due to

retention of phlegm and morbid

fluids;

(b) arteriosclerosis, skin diseases;

(c) high blood pressure,

hepatolienomegaly, neurosis;

(d) angina pectoris;

(e) acute esophagitis;

(f) chronic bronchitis.

or

S. confusum, C. Agardhb

S. fusiforme (Harvey) Setchell ‘‘Yang Xi Cai’’

‘‘Hai Qian’’ S. fulvellum (Turner) C. Agardh ‘‘Wu Lei Ma Wei Zao’’ Used to treat scrofula, goitre, sore

throat, cough and phlegm stasis,

angina pectoris, dropsy, dysuria and

furuncle

‘‘Zhong Hua Ben Cao’’,

and

S. henslowianum, C. Agardh ‘‘Heng Shi Ma Wei Zao’’ ‘‘Guang Dong Zhong Yao

Zhi’’, .

S. thunbergii ‘‘Shu Wei Zao’’

(Mertens ex Roth) Kuntze

S. horneri (Turner) C. Agardh ‘‘Tong Zao’’

Other Sargassum species used in

China (unofficially)c

S. siliquastrum (Turner) C. Agardh ‘‘Lie Ye Ma Wei Zao’’ Similar use as ‘‘Zhong Hua Ben Cao’’,

‘‘Hai Zao’’

S. muticum (Yendo) Fensholt ‘‘Hai Shu Zi’’ and

‘‘Hai Qian’’

S. hemiphyllum (Turner) var. Chinense

J. Agardh

‘‘Ban Ye Ma Wei Zao’’

S. polycystum C. Agardh ‘‘Pu Zhi Ma Wei Zao’’

S.vachellianum Greville ‘‘Wa Shi Ma Wei Zao’’

a Name used in Chinese pharmacopeia (2010 version).b Name used in ‘‘Zhong Hua Hai Yang Ben Cao’’( ) (Guan and Wang, 2009). In this book, S. pallidum C. Agardh and S. confusum C. Agardh are considered as same seaweed used in TCM. But, according to

AlgaeBase (http://www.algaebase.org, last access 29/02/2012), the taxonomic names of these two species are accepted separately.c There are another 8 species listed at ‘‘Zhong Huan Hai Yang Ben Cao’’ , but little chemical and pharmacological information has been found for these species. Therefore, these species have not been listed

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especially the secondary metabolites profiles, between differentSargassum species (Liu et al., 2009). Chemotaxonomic studies ofthis genus would be extremely useful to authenticate the speciesand control the quality of products manufactured from Sargassum.

3. Traditional uses

The ‘‘Shen Nong Ben Cao Jing’’ ( ) or ‘‘Ben Jing’’ ( )provides a summary of early Chinese medicinal knowledge before25–220 AD, and is the first known record of Sargassum seaweed usedto treat goitre or ‘‘Ying Liu’’ ( ) in traditional Chinese medicine.Sargassum has been continuously described as ‘‘Hai Zao’’ ( ) for itstherapeutic uses in ancient Chinese books, such as ‘‘Ming Yi Bie Lu’’( ) or ‘‘Bie Lu’’ ( , written in 220–450 AD), ‘‘Ben Cao ShiYi’’ ( , written in 741 AD) and ‘‘Ben Cao Tu Jing’’ ( ,written in 1061 AD). Although the complete original copies of theseancient books have long been lost, the medicinal uses of Sargassum

seaweeds have been re-examined and written into one of the mostquoted and well kept ancient Chinese medicinal books, the ‘‘Ben CaoGang Mu’’ ( ) or ‘‘Compendium of Materia Medica’’ whichwas written by Shizhen Li in 1578. The Compendium states thatSargassum can soften hard lumps, dispel nodes, eliminate phlegm andinduce urination in humans.

The Sargassum seaweeds or ‘‘Hai Zao’’ ( ) recorded in theCompendium are believed to be S. pallidum (Turner) C. Agardh(‘‘Hai Hao Zi’’, ) and S. fusiforme (Harvey) Setchell (‘‘YangXi Cai’’, ). These two specific species have been listed as‘‘Hai Zao’’ ( ) in the every version of Chinese Pharmacopoeiasince 1953 and indicate confidence in their use as medicinalingredients. According to the modern Chinese pharmacopoeia,‘‘Hai Zao’’ ( ) can be used to treat goitre, scrofula, swelling andpain of testes, oedema due to retention of phlegm and morbidfluids. In modern Chinese medical practise, ‘‘Hai Zao’’ ( ) hasalso been used to treat arteriosclerosis, skin diseases, high bloodpressure, hepatolienomegaly, neurosis, angina pectoris, acuteesophagitis, chronic bronchitis (Table 1) (Editorial Board ofZhong Hua Ben Cao, 1999).

Another four Sargassum species, S. fulvellum (Turner) C.Agardh, S. henslowianum C. Agardh, S. thunbergii (Mertens exRoth) Kuntze, S. horneri (Turner) C. Agardh, commonly named as‘‘Hai Qian’’ ( ) have been used as popular medicines and foodingredients in the south east region of China (Guang Dongprovince, ) (Editorial Board of Zhong Hua Ben Cao, 1999).Similar to the ‘‘Hai Zao’’ ( ), these seaweeds have been used totreat various diseases such as goitre (Table 1). Unofficially,another five species listed in Table 1 may also be used for similartherapeutical purposes as ‘‘Hai Zao’’ ( ) and ‘‘Hai Qian’’ ( ).Although these 11 Sargassum species are used interchangeably,

Table 2Examples of classical Chinese prescriptions containing Sargassum.

Preparationname

Main composition Tra

‘‘Xiao Ying

Wu Hai Wan’’

Laminariae Thallus, Sargassum, Meretricis Concha, Fritillariae

Thunbergii Bulbus, Platycodonis Radix, Prunellae Spica, Citri

Rticulatae Pericarpium, Semen Arecae

Res

tre

‘‘Ru Ji Ling Ke

Li’’

Radix Bupleuri, Rhizoma Cyperi, Pericarpium Citri Reticulatae

Viride, Radix Paeoniae Rubra, Salviae Miltiorrhizae Radix Et

Rhizoma, Vaccariae Semen, Caulis Spatholobi, Concha Ostreae,

Sargassum, Laminariae Thallus, Herba Epimedii, Semen Cuscutae

Dis

sta

to

‘‘Hai Zao Yu

Hu Tang’’

Sargassum fusiforme, Rhizoma pinellia ternate, Fructus Forsythis

suspense, Pericarpium Citrus reticulate, Radix Angelicae sinesis,

Bulbus Fritillariae thunbergii, Rhizoma Ligustici Chuanxiong and

Radix Glycyrrhiza

Rem

har

without comparative chemical and pharmacological profiles it isuncertain that these species can be exchanged.

According to the Chinese Pharmacopeia, a dose of ‘‘Hai Zao’’( ) should be 6–12 g (dry weight) when used as medicine. InTCM, Sargassum seaweeds can be ingested as water decoction oralcoholic tincture, or ground into powder and applied topically(Editorial Board of Zhong Hua Ben Cao, 1999). Sargassum sea-weeds can also be eaten as foods using a small serving. In Japan,S. fusiforme (or Hijiki), named as ‘‘vegetable for longevity’’, is apopular side dish and often prepared by soaking and boiling thedried seaweeds with water and served with soy sauce. Thepopularity of S. fusiforme is spreading to Korea, China, Europeand North America, despite recent warnings for the arseniccontent from several authorities, such as the Government of theHong Kong Special Adminstrative Region (http://www.cfs.gov.hk/,last accessed at 29/02/2012).

Most of Chinese traditional medicines are used in combinationwith other herbs to enrich or enhance the therapeutic functionand reduce side effects. Sargassum seaweeds have been used inmore than 226 prescriptions to treat various diseases in China(http://www.zysj.com.cn, last accessed at 29/02/2012). As most ofChinese traditional medicines, these prescriptions have not beenevaluated using modern evidence-based approaches. Amongthem, ‘‘Xiao Ying Wu Hai Wan’’ ( ) or ‘‘Xiao YingWan’’ ( ) (Table 2) is a prescription having similarity withSargassum’s own traditional therapeutical claims (to treat thyroidrelated diseases) and has been accredited by China State Food andDrug Administration (http://www.sfda.gov.cn/, last accessed at29/02/2012), commercially manufactured and sold in China as amedicine. An opportunity exists to research this prescriptionusing modern scientific methods.

Treating thyroid related diseases, such as simple goitre, is oneof most important traditional uses for Sargassum seaweed. Theiodine in Sargassum seaweed was believed to play an importantrole in the therapeutical function. However the role of iodine mayhave been overestimated and other bioactive metabolites mayhave more significant contribution towards Sargassum’s thera-peutic claims. Recent research on modified decoction of ‘‘Hai ZaoYu Hu Tang’’ ( ) (Table 2) suggested that Sargassum

may play a role as an immunomodulator (Song et al., 2011). Thebioactive metabolites in Sargassum may inhibit thyroid growthinduced by excessive iodine intake and improve immune func-tion, which may be useful in treating Hashimoto’s thyroiditis.

4. Phytochemistry and pharmacological activity

Approximately 80 of the �400 known Sargassum species havebeen analysed for their phytochemical compounds. Although the

ditional and clinical uses Reference

olve hard mass and eliminate goitre, used to

at simple goitre

Chinese Pharmacopoeia

perse stagnated liver qi for relieve qi

gnation, reduce swelling and resolve mass, used

treat mammary gland hyperplasia

Chinese Pharmacopoeia

ove phlegm, relieve qi stagnation, and resolve

d mass, used to treat goitre‘‘Wai Ke Zheng Zong’’

(Summary of Surgical

Medicine) (Song et al., 2011)

http://www.cfs.gov.hk/

http://www.zysj.com.cn

http://www.sfda.gov.cn/

L. Liu et al. / Journal of Ethnopharmacology 142 (2012) 591–619 595

major constituents of the species traditionally used are known,the bioactive secondary metabolites have not been thoroughlystudied. From a chemical prospective, there have been a numberof successful attempts to isolate novel compounds which areabundant in species that are rarely used in traditional medicine(Table 3). These novel compounds may also be present in smallquantities in the species commonly used traditionally but have sofar not been investigated. There is still a lack of effective GC or LCmethods for the phytochemical analysis of Sargassum, which isimportant for the identification of Sargassum species and theeffective quantification of the bioactive compounds.

Diverse pharmacological properties and structurally novelcompounds have been found for the meroterpenoids, pholorota-nins and fucoidans in Sargassum, suggesting that these com-pounds may be the major contributors for the traditionaltherapeutical effects of Sargassum (Table 4). Other compoundssuch as arsenosugars, phytosterols, sulphonoglycolipids, andpolyunsaturated fatty acids have been also reported in the genus(Table 3).

4.1. Meroterpenoids

Meroterpenoids are a class of compounds containing terpenoidelements along with structures of other biosynthetic origin(Cornforth, 1968). Meroterpenoids are particularly abundant inSargassum, which often possess a polyprenyl chain attached to ahydroquinone or similar aromatic ring moiety (Fig. 1). Thesecompounds account for nearly half (�80) of the compoundsidentified in this genus (Table 3). With diverse structures, thisgroup of compounds could be the best candidate for futurechemotaxonomic studies.

d-Tocotrenol, and its 110,120-epoxide were the first meroter-penoids isolated from Sargassum (S. tortile) (Kato et al., 1975).Later many of the meroterpenoids, such as plastoquinones,chromanols and chromenes, were isolated from various species(Table 3 and Fig. 1). Interestingly, the plastoquinones can beeasily converted into the corresponding chromenes by treatingthem with pyridine at room temperature under N2 atmosphere(Iwashima et al., 2005).

These meroterpenoids are structurally related to vitamin E andhave similar biological activities such as antioxidant and antic-ancer activities (Table 4). The meroterpenoids have also beenfound to have in vitro bioactivity such as neuroprotective, anti-malarial and antiviral agents (Tsang and Kamei, 2004; Iwashimaet al., 2005; Afolayan et al., 2008) (Table 4). Recently some in vivo

studies revealed that meroterpenoids in Sargassum may also beused to treat hyperproliferative skin disease, gastric ulcer andcerebral vascular disease (Mori et al., 2006; Hur et al., 2008; Parket al., 2008b) (Table 4). Although meroterpenoids are important inthe context of the medicinal properties of Sargassum, there hasbeen no quantification for these compounds reported in litera-ture. The type and quantity of meroterpenoids in Sargassum mayhave significant impact on the quality of its role as a medicinalingredient. An effective quantification method for the meroterpe-noids in Sargassum needs to be developed to better understandthese compounds and their pharmacological role.

4.2. Phlorotanins

Phlorotanins are tannins found in brown algae that areoligomers of phloroglucinol (1,3,5-trihydroxybenzene). A largenumber (69) of phlorotanins (Table 3) have been identified inSargassum including phlorethols, fuhalols and fucophlorethols(Fig. 2). Although most of these phlorotanins were identified inS. spinuligerum, other species of Sargassum may also contain thesepolyphenols. The size of identified phlorotanins in Sargassum

ranges between 250 (2,30,4,50,6-pentahydroxydiphenyl ether, con-taining 2 phloroglucinol units) and 2644 (eicosafuhalol A, con-taining 20 phloroglucinol units) Daltons, although there must belarger ones that are still unidentified (Glombitza and Keusgen,1995).

When isolating these phlorotainins, the enriched fraction wasoften acetylated immediately with acetic anhydride-pyridine tostabilise the phenols (Glombitza and Keusgen, 1995). For bioac-tivity testing of the isolated pholortainins, a desacetylation can becarried out (Keusgen and Glombitza, 1997). The HPLC methoddeveloped for the isolation of acetylated phlorotainins uses asilica gel column and normal phase solvents, which could beapplied to the analysis and quantification of the phlorotainins inSargassum (Keusgen and Glombitza, 1995). However, an up todate reversed phase HPLC method may be easier and could bedeveloped for the analysis of these polyphenols.

Although the biological activity of individual phlorotaninshave not been studied, the phlorotanins fractions were reportedto have anticoagulant and antioxidant activities (Nakai et al.,2006; Li et al., 2007; Wei et al., 2007, 2003, 2008). Phlorotaninsseparated from S. thunbergii could significantly increase coagula-tion time (in vivo), bleeding time (in vivo), activated partialthromboplastin time (in vitro), prothrombin time (in vitro) andthrombin time (in vitro) and the larger molecular weight phlor-otanins fraction (41�105 Da) have a similar degree of in vivo

and in vitro activity as Aspirin, an antiplatelet drug inhibiting theproduction of thromboxane (Li et al., 2007; Wei et al., 2007).Recent study of the mechanism demonstrated that the antic-oagulant activity of phlorotanins may relate to its ability toreduce the cytosolic calcium level in platelets (Wei et al., 2008).

4.3. Polysaccharides

Polysaccharides are macromolecules with polymeric carbohy-drate structures. The polysaccharides in Sargassum belong tothree major groups, fucoidan, alginate and laminaran. Generally,Sargassum contains more alginate, and less fucodian and lami-naran. However, a large number of bioactive polysaccharidesfound in Sargassum have not been characterised. Both fucoidansand alginates obtained from various Sargassum species werefound to have significantly different mass (8–627 kDa) and, dueto their complexity, the exact structures of bioactive polysacchar-ides have not been fully elucidated.

4.3.1. Fucoidans

Fucoidans, or fucans, are bioactive polysaccharides containingfucose and sulphate which have been mainly identified in brownseaweed (Fig. 3). Diverse fucoidans have been isolated fromSargassum with molecular weight ranging from 5 to 627 kDa.Modern pharmacological research has found that Sargassum

fucoidans have antiviral, anticancer, antioxidant, anti-inflamma-tory, antimicrobial, anticoagulant, hypolipidemic, antivasculo-genic, and liver and renal protective activities (Table 5). Ingeneral, the biological activity of sulphated polysaccharide arerelated to the molecular size, type of sugar and sulphate contentand sulphate position. The type of linkage and molecular geome-try are also known to have a role in its activity.

The fucoidan from Sargassum were found to have antiviralactivity against Herpes Simplex Virus Type 1 (HSV-1), Type 2(HSV-2), Hepatitis A Virus (HAV), coxsackie virus (CVB 3), humancytomegalovirus (HCMV) and Human Immunodeficiency VirusType 1 (HIV-1). The fucoidan can inhibit the initial stages of viralinfection, attachment to and penetration into host cells (Sinhaet al., 2010), and replication stages after virus penetration(Preeprame et al., 2001), however, the exact mechanism remains

Table 3Compounds found in Sargassum seaweed.

Compounds Species Reference

MeroterpenoidsChromequinolide S. sagamianum Horie et al. (2008)

11-Hydroxysargachromelide S. sagamianum Horie et al. (2008)

150-Hydroxysargaquinolide S. sagamianum Horie et al. (2008)

150-Hydroxysargaquinolide; 150-Deoxy, 150 ,160-didehydro S. sagamianum Horie et al. (2008)

2-Methyl-6-(3-methyl-7-oxo-2,5-octadienyl)-1,4-benzoquinone; (E,E)-form S. sagamianum Horie et al. (2008)

Nahocol A S.autumnale Tsuchiya et al. (1998)

100,110-Didehydronahocol A S.autumnale Tsuchiya et al. (1998)

Nahocol A; 130-Ketone, 120R-alcohol S.autumnale Tsuchiya et al. (1998)

Nahocol A; 130-Ketone, 120S-alcohol S.autumnale Tsuchiya et al. (1998)

Nahocol A; 130-Deoxy, 140 ,150-dihydro, 130,140 ,150 ,160-tetradehydro, 120 x-alcohol S.autumnale Tsuchiya et al. (1998)

Nahocol A; 100 ,110-Didehydro(E-), 130-ketone, 120S-alcohol S.autumnale Tsuchiya et al. (1998)

Nahocol A; 100 ,110-Didehydro(Z-), 130-ketone, 120S-alcohol S.autumnale Tsuchiya et al. (1998)

Nahocol A1 S.autumnale Tsuchiya et al. (1998)

Nahocol B S.autumnale Tsuchiya et al. (1998)

Nahocol C S.autumnale Tsuchiya et al. (1998)

Nahocol D1 S.autumnale Tsuchiya et al. (1998)

Nahocol D2 S.autumnale Tsuchiya et al. (1998)

Isonahocol D1 S. autumnale Tsuchiya et al. (1998)

Isonahocol D2 S. siliquastrum Jung et al. (2008)

Isonahocol D1; 120-Ketone S. siliquastrum Jung et al. (2008)

Isonahocol D1; 20E-Isomer, 120-ketone S. siliquastrum Jung et al. (2008)

Isonahocol D1; 20E-Isomer, 100 ,110-dihydro, 120-ketone S. siliquastrum Jung et al. (2008)

Isonahocol D1; 130-Epimer, 60 ,70-dihydro, 60-oxo, 120-deoxy S. siliquastrum Jung et al. (2008)

9,13-Cyclo-3-hydroxy-1,6,10,14-phytatetraen-12-one; [4-Hydroxy-2-

(methoxycarbonylmethyl) phenyl] ether

S. siliquastrum Jung et al. (2008)

2-(12,13-Dihydroxytetraprenyl)-2-(methoxycarbonylmethyl)-5-cyclohexene-1,

4-dione

S. siliquastrum Jung et al. (2008)

Fallachromenoic acid S. fallax Reddy and Urban (2009)

Fallahydroquinone S. fallax Reddy and Urban (2009)

Fallahydroquinone; 1,4-Quinone S. fallax Reddy and Urban (2009)

Mojabanchromanol S. siliquastrum Cho et al. (2008)

Sargachromenol S. serratifolium Kusumi et al. (1979b)

Sargachromanol A S. siliquastrum Jang et al. (2005)

Sargachromanol B S. siliquastrum Jang et al. (2005)

Sargachromanol C S. siliquastrum Jang et al. (2005)

Sargachromanol D S. siliquastrum Jang et al. (2005)

Sargachromanol E S. siliquastrum Jang et al. (2005)

Sargachromanol F S. siliquastrum Jang et al. (2005)

Sargachromanol G S. siliquastrum Jang et al. (2005)

Sargachromanol H S. siliquastrum Jang et al. (2005)

Sargachromanol I S. siliquastrum Jang et al. (2005)

Sargachromanol J S. siliquastrum Jang et al. (2005)

Sargachromanol K S. siliquastrum Jang et al. (2005)

Sargachromanol L S. siliquastrum Jang et al. (2005)

Sargachromanol M S. siliquastrum Jang et al. (2005)

Sargachromanol N S. siliquastrum Jang et al. (2005)

Sargachromanol O S. siliquastrum Jang et al. (2005)

Sargachromanol P S. siliquastrum Jang et al. (2005)

Sargatriol S. tortile Kikuchi et al. (1983)

Sargadiol I S. tortile Numata et al. (1992)

Sargadiol II S. tortile Numata et al. (1992)

Sargathunbergol A S. thunbergii Seo et al. (2007)

Thunbergol A S. thunbergii Seo et al. (2006)

Thunbergol B S. thunbergii Seo et al. (2006)

Sargaquinone S. tortile Ishitsuka et al. (1979)

Sargaquinal S. serratifolium Kusumi et al. (1979b)

Sargaquinoic acid S. serratifolium Kusumi et al. (1979b)

Sargahydroquinoic acid S. sagamianum Segawa and Shirahama (1987)

140 ,150-Dihydroxysargahydroquinone S. micracanthum Iwashima et al. (2005)

Sargahydroquinone; 120-Oxo, 20 ,30-dihydro, 30 ,130-dihydroxy S. siliquastrum Jung et al. (2008)

Sargaol S. tortile Numata et al. (1992)

Sargaol; 110 ,120-Dihydro, 110R,120-dihydroxy S. micracanthum Iwashima et al. (2005)

Sargaol; 90-Oxo, 3,4-dihydro S. micracanthum Iwashima et al. (2008)

Sargaol; 90-Oxo, 3,4,70 ,80b-tetrahydro S. micracanthum Iwashima et al. (2008)

140 ,150-Dihydroxysargaquinone. S. micracanthum Iwashima et al. (2005)

80,90-Dihydroxysargaquinone S. tortile Ishitsuka et al. (1979)

90-Hydroxysargaquinone S. tortile Numata et al. (1992)

110-Methoxysargaquinone S. tortile Ishitsuka et al. (1979)

90-Methoxysargaquinone S. tortile Ishitsuka et al. (1979)

80,90-Dihydroxy-5-methylsargaquinone. S. tortile Ishitsuka et al. (1979)

Sargasal II S. tortile Numata et al. (1992)

Sargasal I S. tortile Numata et al. (1992)

Sargatetraol S. tortile Ishitsuka et al. (1979)

d-Tocotrienol S. tortile Kato et al. (1975)


Table 3 (continued )


d -Tocotrienol; 110 ,120-Epoxide S. tortile Kato et al. (1975)

Yezoquinolide S. sagamianum Segawa and Shirahama (1987)

2,5-Cyclohexadiene-1,4-dione, 2-[(2E,6E,10E)-15-hydroxy-3,7,11,15-tetramethyl-

14-oxo-2,6,10-hexadecatrien-1-yl]-6-methyl-

S. micracanthum Mori et al. (2005)

1,4-Benzenediol, 2-[(2E,6E,10E,14R)-14,15-dihydroxy-3,7,11,15-tetramethyl-

2,6,10-hexadecatrien-1-yl]-6-methyl-


6,10,14-Hexadecatrien-3-one, 16-(2,5-dihydroxy-3-methylphenyl)-2-hydroxy-

2,6,10,14-tetramethyl-, (6E,10E,14E)-


9-Octadecenoic acid (9Z)-, 3-[(2E,6E,10E,14R)-14,15-dihydroxy-3,7,11,15-

tetramethyl-2,6,10-hexadecatrien-1-yl]-4-hydroxy-5-methylphenyl ester


Octadecanoic acid, 3-[(2E,6E,10E,14R)-14,15-dihydroxy-3,7,11,15-tetramethyl-

2,6,10-hexadecatrien-1-yl]-4-hydroxy-5-methylphenyl ester


13-(3,4-dihydro-6-hydroxy-2,8-dimethy-2H-1-benzopyran-2-yl)-2,6,10-

trimethyl-trideca-(2E,6E)-diene-4,5,10-triol.

S. siliquastrum Lee and Seo (2011)

9-(3,4-dihydro-6-hydroxy-2,8-dimethy-2H-1-benzopyran-2-yl)-2,6-dimethyl-

(6E)-nonenoic acid.

S. siliquastrum Lee and Seo (2011)

PhlorotaninsBisfucopentaphlorethol A, 4D-Chloro (or Chlorobisfucopentaphlorethol A) S. spinuligerum Glombitza et al. (1997)

Bisfucotriphlorethol A S. spinuligerum Glombitza et al. (1997)

Bisfucotriphlorethol A; 4D-Hydroxy (or Hydroxybisfucotriphlorethol A) S. spinuligerum Glombitza et al. (1997)

Chlorobisfucopentaphlorethol B S. spinuligerum Glombitza et al. (1997)

Decafuhalol A S. spinuligerum Glombitza and Keusgen (1995)

Difucodiphlorethol A S. spinuligerum Glombitza et al. (1997)

Dihydroxyfucotriphlorethol A S. spinuligerum Glombitza et al. (1997)

Dihydroxyfucotriphlorethol B S. spinuligerum Glombitza et al. (1997)

Dodecafuhalol A S. spinuligerum Glombitza and Keusgen (1995)

Eicosafuhalol A S. spinuligerum Glombitza and Keusgen (1995)

Fucodifucotetraphlorethol A S. spinuligerum Glombitza et al. (1997)

Fucodiphlorethol D S. spinuligerum Glombitza et al. (1997)

Fucodiphlorethol D; 400 0-Hydroxy S. spinuligerum Glombitza et al. (1997)

Fucodiphlorethol E S. spinuligerum Glombitza et al. (1997)

Fucodiphlorethol F S. spinuligerum Glombitza et al. (1997)

Fucophlorethol B S. spinuligerum Glombitza et al. (1997)

Fucophlorethol B; 400 0-Hydroxy S. spinuligerum Glombitza et al. (1997)

Fucotriphlorethol B; 4C,4D-Dihydrox S. spinuligerum Glombitza et al. (1997)

Heptafuhalol A S. spinuligerum Glombitza and Keusgen (1995)

Heptafuhalol A; 2G-Hydroxy S. spinuligerum Glombitza and Keusgen (1995)

Heptafuhalol B S. spinuligerum Keusgen and Glombitza (1995)

Heptafuhalol B; 4B-Hydroxy S. spinuligerum Keusgen and Glombitza (1995)

Hexadecafuhalol A S. spinuligerum Glombitza and Keusgen (1995)

Hexafuhalol A S. spinuligerum Glombitza and Keusgen (1995)

Hexafuhalol A; 4B-Deoxy S. spinuligerum Glombitza and Keusgen (1995)

Hexafuhalol A; 4C-Deoxy S. spinuligerum Glombitza and Keusgen (1995)

Hexafuhalol A; 4E-Deoxy S. spinuligerum Glombitza and Keusgen (1995)

Hexafuhalol A; 4F-Deoxy S. spinuligerum Glombitza and Keusgen (1995)

Hydroxypentafuhalol A S. spinuligerum Glombitza and Keusgen (1995)

Nonafuhalol A S. spinuligerum Glombitza and Keusgen (1995)

S. muticum

Nonafuhalol B S. spinuligerum Keusgen and Glombitza (1995)

Octadecafuhalol A S. spinuligerum Glombitza and Keusgen (1995)

Octafuhalol A S. spinuligerum Glombitza and Keusgen (1995)

Octafuhalol A; 4H-Deoxy S. spinuligerum Glombitza and Keusgen (1995)

Octafuhalol B S. spinuligerum Glombitza and Keusgen (1995)

Octafuhalol C; 4-Deoxy S. spinuligerum Glombitza and Keusgen (1995)

Pentafuhalol A S. spinuligerum Glombitza and Keusgen (1995)

Pentafuhalol A; 2C-Hydroxy S. spinuligerum Glombitza and Keusgen (1995)

Pentafuhalol B S. spinuligerum Glombitza and Keusgen (1995)

2,30 ,4,50,6-Pentahydroxydiphenyl ether S. muticum Glombitza et al. (1978)

S. thunbergii

Pentaphlorethol A S. spinuligerum Glombitza and Keusgen (1995)

Phloroscorbinol S. spinuligerum Keusgen et al. (1997)

Pseudoheptafuhalol A S. spinuligerum Keusgen and Glombitza (1997)

Pseudoheptafuhalol B S. spinuligerum Keusgen and Glombitza (1997)

Pseudoheptafuhalol C S. spinuligerum Keusgen and Glombitza (1997)

Pseudoheptafuhalol D S. spinuligerum Keusgen and Glombitza (1997)

Pseudohexafuhalol A S. spinuligerum Keusgen and Glombitza (1997)

Pseudohexafuhalol B S. spinuligerum Keusgen and Glombitza (1997)

Pseudohexafuhalol C S. spinuligerum Keusgen and Glombitza (1997)

Pseudooctafuhalol B S. spinuligerum Keusgen and Glombitza (1997)

Pseudooctafuhalol C S. spinuligerum Keusgen and Glombitza (1997)

Pseudooctafuhalol D S. spinuligerum Keusgen and Glombitza (1997)

Pseudopentafuhalol A S. spinuligerum Keusgen and Glombitza (1997)

Pseudopentafuhalol B S. spinuligerum Keusgen and Glombitza (1997)

Pseudopentafuhalol C S. spinuligerum Keusgen and Glombitza (1997)

Pseudopentafuhalol D S. spinuligerum Keusgen and Glombitza (1997)




Pseudotetrafuhalol A S. spinuligerum Keusgen and Glombitza (1997)

Pseudotrifuhalol A S. spinuligerum Keusgen and Glombitza (1997)

Tetradecafuhalol A S. spinuligerum Glombitza and Keusgen (1995)

Tetrafuhalol A; 4B-Deoxy S. spinuligerum Keusgen and Glombitza (1997)

Tetrafuhalol A; 4C-Deoxy S. spinuligerum Keusgen and Glombitza (1997)

Tetrafuhalol A; 4D-Deoxy S. spinuligerum Keusgen and Glombitza (1997)

Tetraphlorethol C S. spinuligerum Keusgen and Glombitza (1995)

Tetraphlorethol C; 200 ,4000-Dihydroxy S. spinuligerum Keusgen and Glombitza (1995)

Tetraphlorethol C; 20 ,4000-Dihydroxy S. spinuligerum Keusgen and Glombitza (1995)

Trifuhalol A S. spinuligerum Keusgen and Glombitza (1995)

Trifuhalol A; 4-Hydroxy S. spinuligerum Keusgen and Glombitza (1995)

Trifuhalol B S. spinuligerum Keusgen and Glombitza (1995)

Trifuhalol B; 50-Hydroxy S. spinuligerum Keusgen and Glombitza, (1995)

Undecafuhalol A S. spinuligerum Glombitza and Keusgen (1995)

Phytosterols4(3-2)-Abeo-4-hydroxy-2-oxostigmasta-5,24(28)-dien-3-oic acid; Et ester S. carpophyllum Tang et al. (2003)

3-Hydroxycholest-5-en-24-one; 3b-form, Vinyl enol ether (23Z-) S. thumbergii Kobayashi et al. (1985)

5-Hydroxy-3,4-dinor-2,3-secostigmast-24(28)-en-2,5-olide; (5aOH,24(28)E)-

form

S. carpophyllum Tang et al. (2002)

24-Hydroxystigmasta-4,28-dien-3-one; (24x)-form(Saringosterone) S. asperifolium Ayyad et al. (2003)

Stigmasta-5,23-diene-3,28-diol; (3b,23Z,28x)-form S. carpophyllum Tang et al. (2002)

Stigmasta-5,28-diene-3,24-diol; (3b,24x)-form(Saringosterol) S. asperifolium Ayyad et al. (2003)

Stigmasta-5,22-dien-3-ol; (3b,22E,24S)-form (Stigmasterol) S. asperifolium Ayyad et al. (2003)

Stigmasta-5,24(28)-dien-3-ol; (3b,24(28)E)-form (Fucosterol) S. carpophyllum Wang et al. (1997)

Stigmasta-5,24(28)-dien-3-ol; (3b,20S,24(28)E)-form. (20S- Fucosterol) S. asperifolium Ayyad et al. (2003)

Stigmasta-5,23,25-trien-3-ol; (3b,23E)-form S. polycystum Xu et al. (2002b)

BisnorditerpenesHedaol A Not specified Takada et al. (2001)

Hedaol B Not specified Takada et al. (2001)

Hedaol C Not specified Takada et al. (2001)

14-Hydroxy-2,6,10-trimethyl-10-pentadecen-4-one S. micracanthum Kusumi et al. (1979a)

14-Hydroxy-2,6,10-trimethyl-10-pentadecen-4-one; 5,6-Didehydro S. micracanthum Kusumi et al. (1979a)

Farnesylacetones6,10,14-Trimethyl-5,10-pentadecadiene-2,12-dione; (E, E)-form S. siliquastrum Park et al. (2008a)

6,10,14-Trimethyl-5,10-pentadecadiene-2,12-dione; (E, Z)-form S. siliquastrum Park et al. (2008a)

6,10,14-Trimethyl-5,9-pentadecadiene-2,12-dione; (E, E)-form S. micracanthum Shizuri et al. (1982)

6,10,14-Trimethyl-5,10,13-pentadecatriene-2,12-dione; (E, E)-form S. micracanthum Kusumi et al. (1979a)

6,10,14-Trimethyl-5,9,13-pentadecatriene-2,12-dione; (E, E)-form S. micracanthum Kusumi et al. (1979a)

6,10,14-Trimethyl-5,9,13-pentadecatrien-2-one; (5E, 9E)-form S. micracanthum Kusumi et al. (1979a)

6,10,14-Trimethyl-5-pentadecene-2,12-dione; (E)-form S. micracanthum Kusumi et al. (1979a)

Glycolipids1-O-(6-Deoxy-6-sulphoglucopyranosyl)glycerol; a-D-form, 3-Hexadecanoyl S. wightii Arunkumar et al. (2005)

1-O-(6-Deoxy-6-sulphoglucopyranosyl)glycerol; a-D-form, 3-Octadecanoyl S. thunbergii Son et al. (1992)

Glycerol 1,2-dialkanoates; Glycerol 1,2-dihexadecanoate, 3-O-(6-Deoxy-6-

sulpho-a-D-glucopyranoside)

S. parvivesiculosum Qi et al. (2004)

Glycerol 1,2-dialkanoates; Glycerol 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoate)

2-(9Z,12Z,15Z-octadecatrienoate), 3-O-b-D-Galactopyranoside

S. thunbergii Kim et al. (2007b)

Glycerol 1,2-dialkanoates; Glycerol 1-hexadecanoate 2-(9Z-octadecenoate),

3-O-a-D-Glucopyranoside

S. fulvellum Wu et al. (2009)

Glycerol 1,2-dialkanoates; Glycerol 1-(9Z,12Z,15Z-octadecatrienoate)

2-(6Z,9Z,12Z,15Z-octadecatetraenoate), 3-O-b-D-Galactopyranoside

S. thunbergii Kim et al. (2007b)

Glycerol 1,2-dialkanoates; Glycerol 1-tetradecanoate 2-(9Z-octadecenoate),

3-O-a-D-Glucopyranoside

S.fulvellum Wu et al. (2009)

Arsenosugars2-Amino-3-[[5-deoxy-5-(dimethylarsinoyl)ribofuranosyl]oxy]-1-

propanesulphonic acid; (2S)-b-D-form

S.lacerifolium Francesconi et al. (1991)

Sargassum lacerifolium Arsenomethionine S.lacerifolium Edmonds (2000)

1-O-[5-Deoxy-5-(dimethylarsinoyl)-b-D-ribofuranosyl]-D-mannitol S.lacerifolium Francesconi et al. (1991)

3-[5-Deoxy-5-(dimethylarsinoyl)ribofuranosyloxy]-2-hydroxy-1-

propanesulphonic acid; (2S-b-D)-form


5-Deoxy-5-(dimethylarsinoyl)ribose; b-D-Furanose-form, Me glycoside S.lacerifolium Francesconi et al. (1991)

3-[[(2,3-Dihydroxypropoxy) hydroxyphosphinyl] oxy]-2-hydroxypropyl 5-deoxy-

5-(dimethylarsinoyl) -b-D-ribofuranoside

S.latifolia Francesconi et al. (1991)

2,3-Dihydroxypropyl [5-deoxy-5-(dimethylarsino)] ribofuranoside; As-Oxide,

O30-sulphate


2-Hydroxy-3-(sulphooxy)propyl 5-[[2-carboxy-3-(2,3-

dihydrooxypropoxy)propyl]dimethylarsonio]-5-deoxy-b-D-ribofuranoside

inner salt


2-Hydroxy-3-(sulphooxy)propyl-5-deoxy-5-(trimethylarsonio)-

b-D-ribofuranoside; (20R-b-D)-form

S. thunbergii Shibata and Morita (1988)

Iodoamino acids3-Iodotyrosine (S)-form S. thunbergii Ito et al. (1976)




3,5-Diiodotyrosine; (S)-form S. thunbergii Ito et al. (1976)

3,5,30-Triiodothyronine; (S)-form S. thunbergii Ito et al. (1976)

Thyroxine; (S)-form S. thunbergii Ito et al. (1976)

DipeptidesAurantiamide S. pallidum Liu et al. (2009)

Aurantiamide acetate S. pallidum Liu et al. (2009)

Dia-aurantiamide acetate S. pallidum Liu et al. (2009)

CoumarinsMelanettin S. pallidum Liu et al. (2009)

Stevenin S. pallidum Liu et al. (2009)

FlavonoidsCalycosin S. pallidum Liu et al. (2009)

Liquiritigenin S. pallidum Liu et al. (2009)

DiterpenesSargassinone S. crispum Ayyad et al. (2001)

Crinitol S. tortile Kubo et al. (1985)

LoliolideLoliolide; (6S,7aR)-form S. crassifolium Kuniyoshi (1985)

Loliolide; (6S,7aS)-form S. crassifolium Kuniyoshi (1985)

Octatriene1,3,5-Octatriene; (3E,5E)-form S. horneri Kajiwara et al. (1980)

1,3,5-Octatriene; (3Z,5E)-form S. horneri Kajiwara et al. (1980)

2,4,6-Octatriene; (2E,4Z,6Z)-form S. horneri Kajiwara et al. (1980)

OthersKjellmanianone; (S)-form S. kjellmanianum Nakayama et al. (1980)

1,2-Benzenedicarboxylic acid; Dioctyl ester (Dioctyl phthalate) S. wightii Ehrhardt and Knap (1989)

Zeatin; (E)-form, Deoxy S. heterophyllum Mooney and Van (1987)

Zeatin; (E)-form, 20 ,30S-Dihydro S. heterophyllum Mooney and Van (1987)

4-Methyl-1,2,6,8-tetraazacycloundeca-4,9-diene-3,7,11-trione S. vachellianum Xu et al. (1999)

Sargafuran S. macrocarpum Kamei et al. (2009)

Sargassumketone S. kjellmanianum, S. thunbergii Nozaki et al. (1995)

Sargassumlactam S. jellmanianum Nozaki et al. (1980)

Vernoniether S S. parvivesiculosum Qi et al. (2004)

Mannitol S. mangarevense Zubia et al. (2008)

Fucoxanthin S. horneri Terasaki et al. (2009)

S. thunbergii

S. fusiforme

S. confusum


unknown. In addition, the fucoidan isolated from Sargassum havebeen found to have low cytotoxicity (41000 mg/mL) to virus hostcell lines such as normal Vero cells (African green monkey kidneycells) (Sinha et al., 2010), suggesting the potential for develop-ment of safe antiviral drugs based on these fucoidans.

Since 1970s, a number of animal studies showed fucoidanfrom Sargassum had considerable in vivo anticancer activity andcould significant reduce tumour weight and prolong survival timeof tumour bearing animals (Table 5). However, in vitro experi-ments revealed that Sargassum fucoidans had very limited cyto-toxicity (IC50E0.1–1 mg/mL). Based on the available in vivo andin vitro studies, the anticancer action of Sargassum fucoidans issuspected to be a host-mediated immune mechanism (Itoh et al.,1993; Ale et al., 2011).

Most of Sargassum fucoidans had weaker anticoagulant activitythan heparin, which is a highly sulphated glycosaminoglycansimilar to the structures of fucoidans and widely used as aninjectable anticoagulant. Only Abdel-Fattah et al. (1974) reportedthat fucoidan isolated from S. linifolium had significant higheranticoagulant activity than heparin. Li and Xu (2004) suggestedthe anticoagulant activity of fucoidan isolated from S. fusiforme

had positive correlation with the degree of sulphation, but notwith the molecular weight.

Fucoidans isolated from S. wightii and S. henslowianum werefound to have hypolipidemic effects, reducing serum total cho-lesterol and triglyceride, low-density lipoprotein, and increase

high-density lipoprotein, for mice and rats with the diet-inducedhyperlipidemia (Chen et al., 2010; Preetha and Devaraj, 2010).Interestingly, the fucodians introduced to the animals by sub-cutaneous injection (Preetha and Devaraj, 2010) and gastricperfusion (Chen et al., 2010) both exerted hypolipidemic effects.

In vivo and in vitro anti-inflammatory activity has beenidentified for the fucoidan isolated from S. hemiphyllum andS. wightii (Preetha and Devaraj, 2010; Hwang et al., 2011).Preetha and Devaraj (2010) found the fucoidan isolated from S.

wightii could restore inflammatory complications in rats withdiet-induced hyperlipidemia. The levels of plasma tumour necro-sis factor-alpha (TNF-a), C-reactive protein (CRP), fibrinogen,inducible nitric oxide synthase (iNOS), nitric oxide (NO), cycloox-ygenase-II (COX-2) and lysosomal enzymes could be reduced bytreatment with fucoidan in animal models. Later, Hwang et al.(2011) found fucoidan isolated from S. hemiphyllum could reduceinterleukin (IL)-1b, IL-6, TNF-a, and NO, inhibit mRNA expres-sions of IL-b, iNOS, and COX-2, and down-regulate of NF-kB(nuclear factor kappa-light-chain-enhancer of activated B cells)in nucleus for the mouse macrophage cells (RAW 264.7) activatedby lipopolysaccharide.

4.3.2. Alginates

Alginates are mainly of linear polymers consisting of b-D-mannuronic (M) and a-L-guluronic (G) acids with different M/G

Table 4Major phytochemicals in Sargassum and their pharmacological activities.

Compounds Biologicalactivity

in vivo/in vitro

Model Administration(in vivo)

Dose range ActiveConcentration

Comment Reference

MeroterpenoidsSargaquinoic acid Neuroprot-

ective activity

in vitro Promoted the nerve growth factor (NGF)-induced survival

support on neuronal PC12D cells and abated neuronal PC12D

cell death even in the absence of NGF

– 0 and1.5

mg/mL

1.5 mg/mL Compared in the presence of

0–50 ng/mL NGF in serum free

medium

Tsang and

Kamei

(2004)

in vitro Enhanced neurite-regeneration and protected PC12D cells

from hydrogen peroxide (H2O2)-induced oxidative stress

– 0 and 3 mg/

mL

3 mg/mL

Promote

neurite

outgrowth

in vitro Mechanism study for the neurite outgrowth promotive activity

of Sargaquinoic acid

– 0 and 3 mg/

mL

3 mg/mL Through two separated

signalling pathway

Kamei and

Tsang

(2003)

Anti-

Alzheimer’s

in vitro Inhibitory activity against butyrylcholinesterase – – IC50¼26nM – Choi et al.

(2007)

Treat

hyperprolif-

erative skin

disease

in vitro Synergistic effect with UVB irradiation on the apoptosis of

human keratinocyte HaCaT cells

– 1–5 mg/mL 2 and 5 mg/mL – Hur et al.

(2008)

in vivo On hairless mice with UVB irradiation Topical 0 and 100 mg – Applied 100 mL of 1 mg/mL

sample

Anticancer

activity

in vitro Cytotoxicity against P388 Murine Leukaemia cell line – – IC50¼17 mM – Reddy and

Urban

(2009)

Antimalar-ial

activity

in vitro antiplasmodial activity toward a chloroquine-sensitive strain

(D10) of Plasmodium falciparum

– – IC50¼12.0 mM or

5.1 mg/mL

– Afolayan

et al.

(2008)

Potential

treatment of

metabolic

disorders

in vitro Increased peroxisome proliferator-activated receptors (PPAR)

a/g transcriptional activity in 3T3-L1 cells

– 1–30mM 3–30 mM for PPARa – Kim et al.

(2008a)1–30 mM for

PPARg

Antioxidant

activity

in vitro 1,1-Diphenyl-2-picrylhydrazyl (DPPH) stable free radical

scavenging activity

– – EC50¼27 mg/mL Similar as a-tocopherol with

EC50 of 23 mg/mL

Seo et al.

(2007)

Sargahydroquinoic acid

(similar activities as

sargaquinoic acid not listed)

Selective

vasodilation

effect on the

basilar

arteries

in vivo Selectively accelerate cerebral blood flow through dilatation of

the basilar artery without lowering systemic blood pressure

not specified 10�5.5–

10�4 M

EC50¼11.8mM For carotid artery,

EC50¼140mM

Park et al.

(2008b)

Selective index (SI, EC50 for

carotid/EC50 for basilar):

11.9

Sargachromenol (similar

activities as sargaquinoic acid

not listed)

Promote

neurite

outgrowth

in vitro Showed nerve growth factor (NGF)-dependent neurite

outgrowth promoting activity against PC12D cells

– – ED50¼9mM Promotes neuronal

differentiation and survival of

PC12D cells.

Tsang

et al.

(2005)

Sargachromanols Antioxidant

activity

in vitro Scavenging effects on generation of intracellular reactive

oxygen species (ROS), increments of intracellular glutathione

(GSH) level, and inhibitory effects on lipid peroxidation (LPO)

in human fibrosarcoma HT 1080 cells

– 5 mg/mL for

ROS and

GSH, 50 mg/

mL for LPO

5 mg/mL for ROS and

GSH, 50 mg/mL for

LPO

Most active sargachromanol E

87.2% for ROS

Lee and

Seo (2011)

Inhibit

Naþ/Kþ

ATPase and

isocitrate

lyase

in vitro (a) Naþ/Kþ ATPase and (b) isocitrate lyase inhibitory assay – – (a) IC50¼2.0 mg/ml

(b) IC50¼48.4 mg/ml

Most active Chung

et al.

(2011)

(a) Sargachromanol M

(b) Sargachromanol H

Anticancer

activity

in vitro (a) Inhibited the proliferation of HL-60 cells, and induced

apoptosis, (b) induced apoptosis and (c) downregulated Bcl-xL,

upregulated Bax, activated caspase-3, and cleaved poly (ADP-

ribose) polymerase (PARP)

– a &b: 12.5–

50mM c:12.5

& 25 mM

(a and b) 50mM and

(c) 25 mM

Sargachromanol E isolated

through bioassay-guided

fraction

Heo et al.

(2011)

Nahocol A (most active among

nahocols and isonahocols)

Endothelin

antagonistic

activity

in vitro Inhibition of endothelin (ET-1) binding to its receptors – – IC50¼76.1mM for

ETA, bovine

aorta;IC50¼21.6mM

for ETB, porcine

lung

Potential to treat acute renal

insufficiency, acute

myocardial infarction,

hypertensi-on and

arteriosclerosis.

Tsuchiya

et al.

(1998)

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00

140 ,150-dihydroxysarga-

hydroquinone

Antioxidant

activity

in vitro Antioxidant activities against lipid peroxidation (LPO) and

radical scavenging effect on DPPH

– – IC50¼0.11 mg/mL

for

– Iwashima

et al.

(2005)LPO

IC50¼11.0 mg/mL

for DPPH

140 ,150-dihydroxysarga-

hydroquinone

Prevention of

bone diseases

in vitro (a) inhibition on the differentiation of osteoclast progenitors

into osteoclast-like cells, (b) inhibition of pit formation,

(c) inhibitory effects on the survival of osteoclast-like

cells

– 0–10 mM (a) 3, 6, 10 mM

(b) 6, 10 mM

(c) 6, 10 mM

Potential for prevention of

osteoporosis

Komai

et al.

(2006)

140 ,150-

dihydroxysargaquinone

(similar activities as 140 ,150-

dihydroxysarga-

hydroquinone not listed)

Antiviral

activity

in vitro Antiviral against human cytomegalovirus (HCMV); (a) the

compound was added to the medium during viral infection and

(b) through the incubation

– – CC50¼32 mM a: CC50/IC50¼16 Iwashima

et al.

(2005)

(a) IC50¼2.0 mM

(b) IC50¼2.6 mM

a: CC50/IC50¼12

CC for cytotoxic

Antiulcer

effects

(Gastric)

in vivo hydrochloric acid/ethanol induced rat ulcer Oral 0–30 mg/kg 3–30 mg/kg A decrease in the hexosamine

level of the gastric mucosa

was slightly improved

Mori et al.

(2006)

Intraduodenal 30 mg/kg 30 mg/kg Only one dose reported

110 ,120-Dihydro-110 ,120-

dihydroxysargaol (similar

activities as 140 ,150-

dihydroxysarga-

hydroquinone not listed)

Antiviral

activity

in vitro (a) inhibited early events of human cytomegalovirus (HCMV)

replication including the virus (b) adsorption and

(c) penetration, (d)virucidal action on the virus particles

exposure for 3 h

– (a) 1 and

10 mM

(b) 0–10 mM

(c) 0–10 mM

(d) 0–10 mM

(a) 1 and 10 mM

(b) 0.2 and 1 mM

(c) 0.2 and 1 mM

(d) 0.2–10 mM

Mode of action was evaluated.

Synergistic inhibitors with

ganciclovir, an anti-HCMV

drug

Hayashi

et al.

(2006)

Thunbergol A Antioxidant

activity

in vitro (a) DPPH radical scavenge activity, (b) scavenging activity on

authentic ONOO� , (c) inhibition against the generation of

ONOO� from morpholinosydnonimine

– – (a) EC50¼30 mg/mL

(b) 5 mg/mL

(c) 5 mg/mL

Most active among the

isolated thunbergols

Seo et al.

(2006)

2-Methyl-6-(3-methyl-7-oxo-

2,5-octadienyl)-1,4-

benzoqui-none

Antibacter-ial

activity

in vitro Antibacterial activities against Staphylococcus aureus – – MIC¼2 mg/mL Most active within the

isolated compounds

Horie et al.

(2008)MBC¼64 mg/mL

Meroterphenols A-D Anti-diabetic

(Type 2)

in vitro Induced transcriptional activation of peroxisome proliferator-

activated receptor gamma (PPARg)

– 0–5 mg/mL 5 mg/mL

(active as the

positive control)

Kim et al.

(2011)

Phlorotaninsphlorotanin fraction from S.

thunbergii (MW410,000)

Anticoagul-

ant activity

in vitro Prolonged activated partial thromboplastin time (APTT),

prothrombin time (PT) and thrombin time (TT)

– 0–2 mg/mL 0.5–2 mg/mL Large phlorotanins are active

(in vitro and in vivo).

Li et al.

(2007)

in vivo Increase coagulation time (CT) and bleeding time (BT) in mice Gastric

perfusion

0–40 mg/kg 10–40 mg/kg

in vitro Reduced the elevated platelet cytosolic calcium level induced

by ADP

– 0–2 mg/mL 1 and 2 mg/mL Wei et al.

(2008)

in vivo Prolonged APTT, PT, and TT in rats Gastric

perfusion

0–40 mg/kg 10–40 mg/kg

Phlorotanin fraction from S.

kjellmanianum

Antioxidant

activity

in vitro Scavenging activity against superoxide anion radicals – – IC50¼1.0 mg/mL Nakai et al.

(2006)

in vivo Inhibited the generation of malondialdehyde in mouse liver

and decreased membrane swelling of mouse liver

mitochondria

Oral 5 g/kg 5 g/kg Inhibiting mouse liver lipid

peroxidation. Only single

concentration tested.

Wei et al.

(2003)

PhytosterolsFucosterol (most abundant in

Sargassum)

Cholesterol

lowing

activity

in vivo Inhibited the lymphatic absorption of cholesterol in rats Intragastric 25 mg per

rat

25 mg per rat Only one dose tested Ikeda et al.

(1988)

in vitro Displace cholesterol from bile salt (taurocholate) micelles. – 0.1–2.0 mM 0.1–2.0 mM Equimolar binary mixture

with cholesterol

Anti-diabetic

activity

in vivo Decrease serum glucose concentrations and inhibited of

sorbitol accumulations in the lenses in (a) streptozotocin or

(b) epinephrine-induced diabetic rats

Oral (a) 30

30mg/kg

(b) 0–300

mg/kg

(a) 30 mg/kg

(b) 300 mg/kg

– Lee et al.

(2004)

Anticancer

activity

in vitro Cytotoxicity against P388 cell line – – IC50¼0.7 mg/mL – Tang et al.

(2002)

Antioxidant

activity

in vitro DPPH radical scavenging activity – – IC504250 mM Low in vitro activity Ham et al.

(2010)

in vivo Increased activity of antioxidant enzymes, hepatic cytosolic

superoxide dismutase, catalase and glutathione peroxidase by

in CCl4-intoxicated rats

Oral 30 mg/kg 30 mg/kg Only one dose tested Lee et al.

(2003)

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Compounds Biologicalactivity

in vivo/in vitro

Model Administration(in vivo)


Comment Reference

BisnorditerpenesHedaol B Anticancer in vitro Cytotoxicity against P388 cells – – IC50¼2.2 mg/mL – Takada

et al.

(2001)

Farnesylacetones6,10,14-Trimethyl-5,10-

pentadecadiene-2,12-dione;

(E,E)-form and (E,Z)-form

Vasodilata-

tion effect

in vivo Vasodilatation effect on the (a) basilar and (b) carotid arteries

of rabbits

Not specified (E,E): EC50, (a) 1.22 mM – Park et al.

(2008a)10�6–

10�5 M

(b) 13.7 mM

(E,Z):10�5.5–

10�4.5 M

EC50, (a) 3.72 mM

(b) 14.5 mM

6,10,14-Trimethyl-5,10,13-

pentadecatriene-2,12-dione;

(E,E)-form

Anti-

Alzheimer’s

in vitro (a) Acetylcholinesterase inhibitory activity

(b) Butyrylcholinesterase inhibitory activity

– – (a) IC50 ¼48 mM

(b) IC50 ¼23 mM

– Ryu et al.

(2003)

GlycolipidsGlycerol 1,2-dialkanoates;

Glycerol 1-hexadecanoate 2-

(9Z-octadecenoate), 3-O-a-D-

Glucopyranoside

Fibrinolytic

activity

in vitro Shortened the initiation time of single chain urokinase-type

plasminogen activator activation and increased the rate of

activation,

– 0–15.9 mM Half-maximal effect

at 0.85 mM

more active than the other

glycolipids tested in this

paper

Wu et al.

(2009)

Dipeptidesaurantiamide acetate Antimicro-

bial activity

in vitro Antibiotic against (a) Staphylococcus aureus, (b) S. epidermidis

and (c) Pseudomonas aeruginosa

– 0–0.5 mg/

mL

MIC Concentrations may not be

the final concentration in the

test

Ferreira

et al.

(2004)

(a) 0.1 mg/mL

(b) 0.5 mg/mL

(c) 0.5 mg/mL

Miscellaneous compoundsLoliolides Antioxidant

activity

in vitro (a) DPPH, (b) H2O2 radical and (c) intracellular reactive oxygen

species scavenging, protect H2O2-induced cell damage

– (a, c and d)

0–500 mM,

(b) 0–

250 mM

Active on high

concentrations

No EC50 caculated Yang et al.

(2011)

Sargafuran Antibacterial

activity

in vitro Antibacterial activity against Propionibacterium acnes – – MIC¼15 mg/mL Low cytotoxic to skin cells,

maybe useful for skin care

Kamei

et al.

(2009)

Miscellaneous compoundsFucoxanthin(FC) Anti

infamma-tory

in vitro Decease the expression of cyclooxygenase (COX)-2 and

inducible nitric oxide synthase (iNOS) protein in

RAW264.7cells

– 0–100 mg/

mL

10 and 100 mg/mL Dose-dependent Shiratori

et al.

(2005)

in vitro Reduce the concentrations of nitric oxide (NO), prostaglandin

(PG)-E2 and tumour necrosis factor (TNF)-a–

in vivo Antiinflammation on endotoxin-induced uveitis in rats,

leucocyte and protein infiltration, NO, PGE2 and TNF-aconcentrations in rat aqueous humour

Intravenous

injection

0–10 mg/kg 0.1–10 mg/kg No dose-reponse

Antidiabetic

activities and

anti-obesity

in vivo Decreases the blood glucose and plasma insulin concentrations

of diabetic/obese KK-Ay mice, down-regulate TNF-a and mRNA

in white adipose tissue

Oral Diets with Diets with The combination use of

fucoxanthin and fish oil was

more effective

Maeda

et al.

(2007)

0.1% FC, 0.1% FC,

0.2% FC, 0.2% FC,

0.1%

FCþfish oil

0.1% FCþfish oil

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An

tica

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–(a

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5.2

(b)

0–

22

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(c)

22

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(d)

FC

3.8þ

TG

10

( mM

for

all

)

(a)

7.6

an

d1

5.2

(b)

11

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nd

22

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(c)

22

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(d)

FC3

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TG

10

for

48

h( m

Mfo

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(a)

mo

rea

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et

al.

(20

04

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inv

itro

For

HL-

60

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ep

G-2

an

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t-2

9ce

lls,

ind

uct

ion

on

the

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cie

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nd

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uce

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po

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AR

P)

an

dd

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ea

seo

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ls

–0

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(20

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(b)

0–

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(e)

5–

50

(mg

/mL)

(e)

50mM

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0.1

–2

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.14

mg

/mL

(d)

0.2

5–

0.5

(d)

2.5

mg

/mL


ratios and linear arrangements (Fig. 3). As alginates can absorbwater and form viscous gum, they have been used as thickeners,stabilisers and gelling agents in the food and pharmaceuticalindustries. Alginates have been considered to be without anynutritional value, however, modern pharmacological researchfound alginates isolated from Sargassum had anticancer (in vivo),antiviral (in vitro) and hypolipidemic (in vivo) activity (Table 5).It is important not to overlook these pharmacological effects, asthese bioactive alginates may confer health benefits or risks to themany people who consumed them regularly as food additives.

The alginates from the genus Sargassum were found to have awide range of molecular weights (13–330 kDa) (Table 4), which maydepend upon the species, season, age, part of plant used for extractionand the extraction method. Alginates are water soluble, so they canbe extracted directly by hot water. Sodium alginates form insolubleprecipitates at acidic pH and with calcium salts, but they are stable insolution between pHs 6 and 9. Therefore, the alginates were oftenextracted with K2CO3, which can significantly increase the yield.Interestingly, the alginates directly extracted from Sargassum speciesusing hot water often had lower molecular weights (13–33.4 kDa)(Fujihara et al., 1984a, 1984b; Gu et al., 1998; Mao et al., 2004). Whilethe base digestion often yielded significantly larger alginates (194–330 kDa) (Fujihara and Nagumo, 1992; Sousa et al., 2008, 2007).Therefore, we suspect that the small MW alginates may be in theintercellular space and relatively easy to extract compared to thelarge alginates, which form parts of the cell walls of the brown algae.Comparison of the biological activity between these small and largealginates requires investigation and details about the extract’s com-position need to be included in such studies.

4.4. Other compounds

Other compounds reported in Sargassum include phytosterols,bisnorditerpenes, farnesylacetones, polyunsaturated fatty acids,glycolipids, arsenosugars, dipeptides, iodoamino acids, loliolides,octatrienes, etc. (Table 3). Compared to the meroterpenoids,phlorotanins, polysaccharides in Sargassum, there are fewerreports on these constituents.

4.4.1. Phytosterols

Phytosterols such as saringosterol and fucosterol have beenidentified in some species (Wang et al., 1997; Ayyad et al., 2003).Fucosterol, a characteristic component of brown seaweeds, wasfound to be the major phytosterols (485%) in S. despiense,

S. latifolium and S. carpophyllum (Karawya et al., 1987; Wang et al.,1997). Fucosterol could inhibit the cholesterol absorption in rats bydisplacing cholesterol from bile salt micelles (Ikeda et al., 1988)(Table 4). Although fucosterol had very low in vitro antioxidantactivity (Ham et al., 2010), it exhibited in vivo antioxidant activity byincreasing activity of antioxidant enzymes such as hepatic cytosolicsuperoxide dismutase, catalase and glutathione peroxidase in CCl4-intoxicated rats (Lee et al., 2003). Fucosterol was also identified asan antidiabetic compound (Lee et al., 2004). When administeredorally, fucosterol decreased serum glucose concentrations andinhibited sorbitol accumulations in the lenses of diabetic rats.

4.4.2. Bisnorditerpenens and farnesylacetones

With similar structures, some bisnorditerpenes and farnesyla-cetones have been identified in Sargassum (Kusumi et al., 1979a;Shizuri et al., 1982; Takada et al., 2001) (Fig. 4). So far, onlycytotoxicity has been reported for the bisnorditerpenes such ashedaols A, B, and C in Sargassum (Takada et al., 2001). Farnesy-lacetones in Sargassum showed a moderate in vivo vasodilatationeffect on the basilar arteries of rabbits (Park et al., 2008a) and

O

HO O

O

O OH

Sargaquinoic acid

OH

OH

O OH

Sargahydroquinoic acidO

HOOOH

Sargachromenol

HO

OOH

OH

Sargachromanol E

OH

O

O

HO

O O

Nahocol A

OH

OH

OH

OH

14', 15'- dihydroxysargahydroquinone

O

HOOH

OH11', 12'-Dihydro-11',12'-dihydroxysargaol

O

HOOOH OH

Thunbergol A

δ-Tocotrienol

Fig. 1. Structures of meroterpenoids.

O O

HOHOHO

HO OH

HO HO HO

OH

O

OH

HO OH

OH

O

HO OH

OH

OH

HO

HO

OO

HO

HOHO

O

HOHO

HO

OH

HO

HO

O

OH

HO

OHHO

HO

Fig. 2. Structures of simple phlorotanins.


some potential to treat Alzheimer’s disease with in vitro choli-nesterase inhibitory activity (Ryu et al., 2003).

4.4.3. Polyunsaturated fatty acids and glycolipids

Sargassum is also a rich source of polyunsaturated fatty acids andglycolipids, which are functional lipids with proven nutritional

significance (Sanina et al., 2004). Long-chain omega-3 and -6 fattyacids such as eicosapentaenoicacid (EPA, 20:5n-3), arachidonic acid(AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3) are particu-larly rich in some Sargassum species (Terasaki et al., 2009; vanGinneken et al., 2011). Glycolipids in Sargassum includes glucosyl-glycerols, galactosylglycerols and sulphonoglycolipids (Son et al.,1992; Qi et al., 2004; Arunkumar et al., 2005; Kim et al., 2007b;

O OOCH

O3SO

OO

OHCH

O3SO

OH

O OOHOH

O OOHOH

O

O

OHOH

COOH

COOH

COOH

O

O

OHOHCOOH

O

L-guluronic acids

D-mannuronic acids

Fig. 3. Structures of fucoidan and alginate.


Wu et al., 2009). Some glucosyldiacylglycerols in S. fulvellum showedfibrinolytic activity in the reaction system of single chain urokinase-type plasminogen activator and plasminogen (Wu et al., 2009). Todate, the understanding of the pharmacological activity of theglycolipids in Sargassum is limited.

4.4.4. Arsenosugars

Like many marine algae, Sargassum seaweeds contain arseno-sugars that are arsenic-containing ribofuranosides (Fig. 4)(Table 3). As arsenosugars may be hazardous to human health(Andrewes et al., 2004), the level of arsenosugars in differentSargassum species used in TCM needs to be further studied andappropriately quantified.

4.4.5. Iodoamino acids

Iodoamino acids such as monoiodotyrosine (MIT), diiodotyr-osine (DIT), triiodothyronine (T3) and thyroxine (T4) have beenidentified in S. thunbergii (Ito et al., 1976). The level of MIT andDIT was much higher than T3 and T4 in S. thunbergii. T3 and T4are the same hormones produced by the thyroid gland central tometabolic regulation, which are also clinically significant forGrave’s disease and Hashimoto’s thyroiditis (Michelangeli et al.,2000). In human thyroid, T4 is produced by combining twomoieties of DIT, and T3 is produced by combining one moleculeof MIT and one molecule of DIT. MIT and DIT were formed bycovalently bound iodine to tyrosine residues in thyroglobulin (Tg)molecules via a reaction with the thyroperoxidase (TPO) (Ekholmand Bjorkman, 1997). It is possible that some compounds mediat-ing the iodoamino acids in Sargassum may affect human thyroidmetabolism, and contribute to a traditionally observed pharma-cological effect in thyroid disease.

4.4.6. Dipeptides

Three dipeptides, aurantiamide, aurantiamide acetate and dia-aurantiamide have been isolated from S. pallidum (Liu et al., 2009).Although aurantiamide acetate was found to have antibiotic activityagainst Staphylococcus aureus, S. epidermidis and Pseudomonas

aeruginosa (Ferreira et al., 2004), little pharmacological study hasbeen done on these dipeptides from Sargassum.

4.4.7. Flavonoids and coumarins

Two flavonoids, calycosin and liquiritigenin and two coumar-ins, melanettin and stevenin have been isolated from S. pallidum

(Liu et al., 2009). The levels of these compounds in Sargassum

may be very low and the exact values are unknown. Flavonoidsand coumarins are commonly known as bioactive compounds(Mabry and Ulubelen, 1980) but their contribution to pharmaco-logical activity of Sargassum may be very limited due to their lowconcentrations.

4.4.8. Miscellaneous compounds

Loliolides (2), octatrienes (3), kjellmanianone, zeatins (2),4-methyl-1,2,6,8-tetraazacycloundeca-4,9-diene-3,7,11-trione,sargafuran, sargassumketone, sargassumlactam, vernoniether S,mannitol, fucoxanthin have been also identified in Sargassum

(Fig. 4). Loliolides have been identified in S. crassifolium

(Kuniyoshi, 1985) and they had moderate in vitro antioxidantactivity and showed protective effect for cells against H2O2-induced cell damage or apoptosis (Yang et al., 2011). Sargafuranwas identified in S. macrocarpum with antibacterial activityagainst Propionibacterium acnes, which can be developed intonew skin care cosmetics to prevent or treat acne (Kamei et al.,2009).

Mannitol is commonly found in brown seaweeds, where it isthe primary product from photosynthesis (Zubia et al., 2008).Sargassum contains very high level of mannitol, e.g. 12.2% dryweight in S. mangarevense. This polyol has osmotic diuretic effectand is a weak renal vasodilator (Better et al., 1997). The highmannitol content may induce urination and reduce oedema,which are part of the traditional claims for Sargassum.

Fucoxanthin is a carotenoid in the chloroplasts of brown algaeand has been identified in several Sargassum species (Terasakiet al., 2009). Recent pharmacological research indicates thatfucoxanthin had anticancer, anti-inflammatory, antioxidant, anti-obesity and antidiabetic activities (Hosokawa et al., 2004;Shiratori et al., 2005; Maeda et al., 2007; Sachindra et al., 2007;Kim et al., 2010). Sargassum contain 1–8 mg of fucoxanthin per gof dry weight with seasonal variation (Terasaki et al., 2009).This compound may make a significant contribution to thetraditionally observed therapeutical effects of Sargassum.

5. Pharmacological properties of Sargassum extracts

The extracts of many seaweeds species have been screened fortheir pharmacological activity. Among them, Sargassum spp.extracted using various solvents showed anti-inflammatory,anti-allergic, antimicrobial, antiviral, antiplasmodial, anticancer,hypoglycaemic, liver protective, gastric protective, bone protec-tive, skin-whitening, anti-Alzheimer’s and antioxidant activities(Table 6). In these reports, the bioactive compounds responsiblefor these effects have not been identified. We have examined theactivities of these extracts against the bioactive metabolitesoutlined in Section 4 and extrapolate likely responsible com-pounds and make suggestions for further investigation.

5.1. Anti-inflammatory activity

The relatively lipophilic extracts such as hexane, dichloro-methane and 95% ethanol extracts of Sargassum showed in vitro

and in vivo anti-inflammatory activity (Dar et al., 2007; Kang

Table 5Bioactive alginates and fucoidan from Sargassum.

Polysacc-harides

Biologicalactivity

in vivo/in vitro Model Administration(in vivo)


Comment MW Reference

AlginatesAnticancer

activity

in vivo Inhibited growth of sarcoma 180 in

mice, led to acute tubular necrosis and

cause the enlargement of the white

pulp of the spleen

intraperitone-

ally or orally

0–100

m/m2/day

50 and 100

m/m2/day

Alginates with

different

viscosity tested

194, 330 kDa Sousa et al.

(2007)

in vivo Prolonged the survival duration of mice

suffering from ascetic Sarcome 180

through intraperitoneal injection

Intraperitoneal

injection

0, 75 mg/kg 75 mg/kg Only one dose

tested

13 kDa Gu et al.

(1998)

in vivo Increase life span for mice with

sarcoma-180 and Ehrlich ascites

carcinoma or IMC carcinoma.

Intraperitoneal

injection

0–100 mg/kg 12.5–100 mg/kg – 29kDa Fujihara et al.

(1984b)

in vivo Reduced size of subcutaneous Sarcoma-

180 carcinoma tumour in mice

Intraperitoneal

injection

0–50 mg/kg 10–50 mg/kg – 33.4 kDa Fujihara et al.

(1984a)

Antiviral

activity

in vitro antiviral against Herpes Simplex Virus

Type 1.

– – IC50 ¼15 mg/mL – 2675 kDa Sinha et al.

(2010)

Hypolipid-emic

activity

in vivo Decreased total cholesterol, triglyceride

and low density lipoprotein-cholesterol

and increase the high density

lipoprotein-cholesterol.

Gastrointestinal

injection


tested

16 kDa Mao et al.

(2004)

Renal effect in vitro Increased perfusion pressure, renal

vascular resistance, glomerular filtration

rate, urinary flow and sodium,

potassium and chloride excretion and by

reduction of chloride tubular transport.

– 10 mg/mL 10 mg/mL Alginates with

different

viscosity tested

194, 330 kDa Sousa et al.

(2008)

FucoidansAnticancer

activity

in vitro Inhibited the growth of RPMI-7951

human melanoma cells

– 0–200 mg/mL 200 mg/mL. Only 28%

inhibiton at

200 mg/mL

n/a Sokolova et al.

(2011)

in vitro Inhibited (a) colony formation in human

melanoma (SK-MEL-28) and (b) colon

cancer cells (DLD-1)

– 100 mg/mL 100 mg/mL Low

cytotoxicity

found

n/a Ermakova

et al. (2011)(a) 15–32%

(b) 32%–44%

Anticancer

activity

in vitro Induced apoptosis by mitochondrial

release of apoptosis-inducing factor into

cytosol in HeLa cells, decreased the

expression of anti-apoptotic protein

Bcl-2 and increased expression of

apoptogenic protein Bax

– 1.5 mg/mL 1.5 mg/mL Mechanism

study, only one

concentration

tested.

n/a Costa et al.

(2011b)

in vitro Inhibited (a) HepG2, (b) PC3 and

(c) Hela cells

– 0.1–2.0 mg/mL a: 38%&b: 31%

at 2 mg/mL

c:IC50¼13mM

Five fucoidan

fractions tested

n/a Costa et al.

(2011a)

in vivo Induced enhanced natural killer cell

activity in mice

Intraperitoneal

injection


test

n/a Ale et al.

(2011)

in vitro Reduced (a) Lewis Lung Carcinoma cell

and (b) melanoma B16 cells cell

viability

– 0–1 mg/mL (a) 40%, 1 mg/

mL

(b) 20%, 1 mg/

mL

–

L.Liu

eta

l./

Jou

rna

lo

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thn

op

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gy

14

2(2

01

2)

59

1–

61

96

06

in vitro Antiproliferative activity on Hela cells – 0–2 mg/mL 61% inhibition

100 mg/mL

– n/a Costa et al.

(2010)

in vitro Inhibited growth of HepG2 cells, A549

cells, and MGC-803 cells

– 0–1 mg/mL 1 mg/mL (50%–

81.4%)

Low in vitro

activity

o50 kDa Ye et al.

(2008)

in vitro Inhibited the growth of (a) human

Rhabdosarcoma cells and (b) lung

cancer cells by fucoidan fraction 20.

Inhibited lung cancer cells by fucoidan

fraction 25

– IC50, a:16.6,

b:13.4, c:13.8

(mg/mL)

4100 kDa Nguyen et al.

(2008)

in vivo Inhibited the growth of S180 tumor in

mice and enhanced the functions of the

immune organs, increase SOD content

and glutathione peroxidase activity,

decrease malondialdehyde content

Intraperitoneal

injection

0, 75, 150 mg/kg 150 mg/kg – n/a Liu and Meng

(2004)

in vitro Inhibited the growth of SPCA-I lung

cancer cell,

– 0–1.2 mg/mL IC50¼423

mg/mL

Low in vitro

activity

n/a Liu et al.

(2003)

in vitro Promoted accentuated morphologic

modifications in HeLa cells, caused

alterations in the cellular morphology

and reduction of the growth, increased

in the number of condensed cells,

atypical nuclei, number of clusters and

blebs at

– 1.25–160 mg/mL 40 mg/mL – n/a Stevan et al.

(2001)

Anticancer

activity

in vivo Prolonged the survival duration of mice

with Ehrlich carcinoma transplanted

Intraperitoneal

injection

0, 20 mg/kg 20 mg/kg – 19,13.5 kDa Zhuang et al.

(1995)

in vivo Inhibited lung metastases induced by

Lewis lung carcinoma

Intraperitoneal

injection

0–50 mg/kg 20 mg/kg when using

with

5-fluorouracil

19 kDa Itoh et al.

(1995)

in vivo Activated the reticuloendothelial

system, enhanced the phagocytosis and

chemiluminescence of macrophages in

mice

Intraperitoneal

injection


tested

19 kDa Itoh et al.

(1993)

in vivo Prolonged the survival duration mice

with Sarcoma-180 ascites tumor.

Intraperitoneal

injection

0–50 mg/kg 50 mg/kg – n/a Nagumo et al.

(1988)

in vivo Prolonged the survival duration mice

with Sarcoma-180 ascites tumor

Intraperitoneal

injection

0–250 mg/kg 25 mg/kg Toxic at high

concentration

n/a Iizima-Mizui

et al. (1985)

in vivo Fucoidan and sulphated fucoidan

fraction enhance antitumor activity

against L-1210 leukemia, increase life

span

Intraperitoneal

injection

0–300 mg/kg 300 mg/kg Sulphated

fucoidan more

active

n/a Yamamoto

et al. (1984)

in vivo Reduced Sarcoma-180 tumor Intraperitoneal

injection

50 mg/kg for the

active Fr.

50 mg/kg Only one

concentration

tested

n/a Yamamoto

et al. (1977)

Anticoagul-ant

activity

in vitro Anticoagulant with relative clotting

factor of 27.47 for the fucoidan

– 0–180 mg/mL 180 mg/mL Activity weaker

than heparin.

8–20 kDa De et al.

(2008)

in vivo Anticoagulant with when in mice Intravenous

injection

10 mg/

mL�0.1 mL/g

10 mg/

mL�0.1 mL/g

76% of heparin

equivalents

n/a Liu et al.

(2004)

in vitro Prolonged activated partial

thromboplastin time

– 0–100 mg/mL 5–100 mg/mL weaker than

heparin

25–950 kDa Li and Xu

(2004)

in vitro The required time for the clotting of

blood plasma of the isolated fucoidan

– 1% 1% Fucoidan 72h,

Heparin: 1 h.

n/a Abdel-Fattah

et al. (1974)

Anti-inflammat-

ory activity

in vitro Reduced IL-1beta, IL-6, TNF-a, and NO

in the mouse macrophage cell line

(RAW 264.7) activated by

lipopolysaccharide. Inhibited mRNA

expressions of IL-beta, iNOS, and COX-2.

Down-regulated of NF-kB in nucleus

– 0–5 mg/mL 5 mg/mL Active at high

concentration

n/a Hwang et al.

(2011)

in vivo Restore inflammatory complications in

rats with diet-induced hyperlipidemia.

Subcutaneous

injection

0, 5 mg/kg 5 mg/kg n/a

L.Liu

eta

l./

Jou

rna

lo

fE

thn

op

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rma

colo

gy

14

2(2

01

2)

59

1–

61

96

07


Polysacc-harides

Biologicalactivity

in vivo/in vitro Model Administration(in vivo)


Comment MW Reference

Anti-

inflammatory

activity

Reduced levels of plasma TNF-a,

C-reactive protein, fibrinogen, iNOS, NO,

COX-2 and lysosomal enzymes

Only one

concentration

tested

Preetha and

Devaraj

(2010)

Antioxidant

activity

in vitro (a) Total antioxidant capacity,

scavenging (b) hydroxyl and

(c) superoxide radicals, (d) reducing

power and (e) ferrous ion chelating

– (a) n/a (b and c) 0.5 (a) 90.7 ascorbic

acid equivalents

n/a Costa et al.

(2011a)(b and c) 0.05–

0.5

(d) 0.5

(d) 0.01–0.5 (e) 2.0 mg/mL

(e) 0.1–2.0

mg/mL)

in vitro Antioxidant with (a) DPPH, H2O2, NO

radical scavenging activity and (b) H2O2

scavenging activity in V79-4 cells

– (a) 10 mg/mL

(b) 0–10

mg/mL

(a) 10 mg/mL

(b) 5 mg/mL

low activity 529 kDa Kim et al.

(2007a)

in vitro DPPH radical scavenging activity – 1–5 mg/mL – low activity o50 kDa Ye et al.

(2008)

Antiviral

activity

in vitro Antiviral against Herpes Simplex Virus

Type 2 (HSV-2) (a) during infection and

throughout the incubation;

(b) immediately after viral infection

– – IC50 CC50/IC50 19.8 kDa Lee et al.

(2011)(a) 18 mg/mL

(b) 410

mg/mL

(a) 4280

(b) 412

in vitro Antiviral against Herpes Simplex Virus

Type 1 (HSV-1)

– 0–100 mg/mL IC50¼1.4 mg/mL CC5041000

mg/mL

3075 kDa Sinha et al.

(2010)

in vitro Inhibition against (a) HSV-1 and

(b) Hepatitis A Virus (HAV)

– 0–40 mg/mL 40 mg/mL,

a:81%, b:85%

Active depends

on degree of

sulphation and

MW

70–130 kDa Asker et al.

(2007)

in vitro Antiviral against HSV-1 – 0–25 mg/mL EC50¼1.5–5.3

mg/mL

Inhibit

attachment of

virus to cells

424 kDa Zhu et al.

(2006)

in vitro Antiviral against HSV-2, against HSV-2

strain 8702 and clinical strain for virus

adsorption

– 0–100 mg/mL EC50¼1.85 and

3.5 mg/mL

Inhibit virus

adsorption

n/a Zhu et al.

(2004)

in vitro Kill HSV-1 and coxsackie virus (CVB 3) – – IC50¼0.8–

50 mg/mL

CC5045000

mg/mL

n/a Cen et al.

(2004)

Antiviral

activity

in vitro Antiviral against HSV-2, HSV-1, and

HSV-1 acyclovir resistant strain

– – 1.3, 5.5, and

4.1 mg/mL

CC5044000

mg/mL

424 kDa Zhu et al.

(2003)

in vitro Antiviral against HSV-1, added to the

medium (a) at the same time as the

viral infection, (b) after viral infection

– – CC50/IC50

(a) 11,000 and

(b) 7100

– 270 kDa Preeprame

et al. (2001)

in vitro Antiviral against (a) HSV-1, (b) human

cytomegalovirus (HCMV) and

(c) Human Immunodeficiency Virus

Type 1 (HIV-1)

– – IC50, (a) 1.0,1.4;

(b) 3.3, 8.5;

(c) 1.2, 5.4

(mg/mL)

CC5042440–

6200 mg/mL

229 kDa Hoshino et al.

(1998)

Hyoplipid-emic in vivo Reduced total cholesterol and

triglyceride, reduce LDL and VLDL,

elevate HDL in mice

Subcutaneous

injection


tested

n/a Preetha and

Devaraj

(2010)

in vivo Reduce total cholesterol and

triglyceride, reduce LDL and VLDL,

elevate HDL in mice

Gastric

perfusion

0–200 mg/kg 50–200 mg/kg – n/a Chen et al.

(2010)

L.Liu

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mg

/kg

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et al., 2008; Lee et al., 2008). The in vivo anti-inflammatoryactivity can be observed through both topical application andintraperitoneal injection of the extracts. Although fucoidan fromSargassum showed in vivo and in vitro anti-inflammatory activity(Preetha and Devaraj, 2010; Hwang et al., 2011), this hydrophilicpolysaccharide is unlikely to be responsible for the anti-inflam-matory activity of the lipophilic extracts. The anti-inflammatoryactivity in these lipophilic extracts is more likely to be attributedto the liopophilic components such as phytosterols, polyunsatu-rated fatty acids, fucoxanthin and meroterpenoids. The constitu-ents need to be evaluated in further anti-inflammatory research.

5.2. Anti-allergic activity

In vitro studies on mast cells indicated the anti-allergicpotential of Sargassum extracts (Na et al., 2004, 2005; Lee et al.,2006), which might be useful to allergic diseases like atopicdermatitis. Sargasssum extracts (at a relatively high concentrationof 100 mg/mL) exerted moderate inhibitory activity (about 50%)against compound 48/80-induced histamine and b-hexosamini-dase release from rat peritoneal mast cells (Na et al., 2004; Leeet al., 2006). In vivo study suggested that oral administration ofSargassum extract could protect mice from the IgE-mediated localallergic reaction (Na et al., 2005). NMR analysis suggested that theactive compounds had sugar moieties and long aliphatic chainslike glycolipids (Na et al., 2005), which requires furtherinvestigation.

5.3. Antimicrobial, antiviral and antiplasmodial activities

Sargassum extracts have broad antimicrobial activities againstbacteria and fungi (Morales et al., 2006). The lipophilic fraction(ethyl acetate) of extracts showed stronger antimicrobial activitythan the hydrophilic components (water). The activity may beattributed to meroterpenoids such as 2-methyl-6-(3-methyl-7-oxo-2,5-octadienyl)-1,4-benzoquinone (Horie et al., 2008).

Sargassum extracts exerted in vitro antiviral activities againstHuman T-cell Lymphotropic Virus Type 1 (HTLV-1) (Romanoset al., 2002), Human Immunodeficiency Virus Type 1 (HIV-1) (Ahnet al., 2002) and vaccinia virus (Premanathan et al., 1994). Theantiviral activity of HTLV-1 by S. vulgare water extract is likely tobe linked to the fucoidan (Table 5). The antiviral activity againstHIV-1 and vaccinia virus need to be further researched and thepotential for novel antivirals from Sargassum determined.

In vitro screening of seaweeds for promoting production ofinterferon b (INF-b), which has strong antiviral effect by inducingantiviral action in cells susceptible to viruses, suggested methanolextract of S. hemiphyllum had antiviral activity (Nakano et al.,1997). Two active substances with less than 3000 molecularweight, heat stable and noncytotoxic characters were identifiedbut the structures were not elucidated. The more active com-pound showed in vivo antiviral activity for mice infected withAujeszky’s disease virus (Nakano and Kamei, 2005), which nowneeds to be characterised.

The dichloromethane fraction of a dicholormethane/methanolextract of S. hemiphyllum exerted potent in vitro antiplasmodialactivity (IC50¼2.8 mg/mL) against Plasmodium falciparum (Lateganet al., 2009). The activity of this lipophilic fraction is likely due tothe bioactive meroterpenoids like sargaquinoic acid (Afolayanet al., 2008). In vivo studies are required to evaluate the anti-plasmodial potential of Sargassum.

5.4. Anticancer activity

In vitro and in vivo studies suggested Sargassum extracts hadanticancer activity (Table 6). Khanavi et al. (2010) found the

Fig. 4. Structures of other compounds in Sargassum.


hexane fraction of methanol extract of S. swartzii had in vitro

cytotoxicity against Caco-2 and T47D cells and increased thepercentage of apoptotic cells among these cells. The activity of

this lipophilic fraction may in part be due to the meroterpenoids(Table 4), which needs to be investigated further. Most anticancerstudies were carried out using the Sargassum water extracts


(Yamamoto et al., 1981, 1974; Matsuda et al., 2005; Zandi et al.,2010). which exerted in vitro and in vivo anticancer activities andin vivo activity can be observed in both oral administration andintraperitoneal injection of Sargassum water extracts. The in vivo

anticancer activity may be attributed to active polysaccharides(Table 5), but there may be other smaller active constituents, asthe intact polysaccharides are poorly absorbed through oraladministration.

5.5. Liver and bone protective activities

Sargassum extracts have potential to protect vital organs suchas liver and bone. In vivo studies suggested oral administration ofSargassum ethanol or water extracts can protect rat liver fromacetaminophen induced toxic hepatitis and hepatic oxidativestress, and reduced CCl4 induced acute elevation of serumglutamic pyruvic transaminase (GPT) and glutamic oxaloacetictransminase (GOT) in rats (Wong et al., 2000; Raghavendran et al.,2006, 2004b). The doses ranges tested in these studies were verylimited and the active dose reported was very high (200–600 mg/kg). More recently, Raghavendran et al. (2007) researched thepolysaccharides fraction of Sargassum extract and suggested thehepatoprotective activity was due to the bioactive fucoidan.

A series of in vitro and in vivo studies suggested S. horneri

water extracts has anabolic effects on bone calcification in ratfemoral tissues (Yamaguchi et al., 2001; Uchiyama andYamaguchi, 2002a, 2002b, 2003; Uchiyama et al., 2004). Oraladministration of S. horneri water extracts could prevent boneloss and stimulate bone calcification in rats (Yamaguchi et al.,2001; Uchiyama and Yamaguchi, 2003). In vitro study of S. horneri

water extracts revealed two active components promoting boneprotection (Uchiyama et al., 2004). One active component increas-ing calcium content was identified with approximate molecularweight of 1000 but this compound was not heat stable (80 1C for30 min) and its structure has not been elucidated. The other heatstable component suppressing osteoclastic bone resorption(molecular weight more than 50,000) was speculated to be apeptide. Further research is needed to elucidate the structures ofthese compounds. To date, 140,150-dihydroxysargahydroquinoneand other meroterpenoids have been identified in Sargassum

suppressing bone resorption (Komai et al., 2006), which maycontribute the bone protective activity of Sargassum extracts.

5.6. Other pharmacological activity

Other pharmacological activity of Sargassum extracts includeskin-whitening, anti-Alzheimer’s, hypoglycaemic, gastric protectiveand antioxidant activities (Table 6). Sargassum extract exerted in vitro

inhibitory activity against tyrosinase and melanin production (Chaet al., 2011; Chan et al., 2011), which could be developed to a skin-whitening agent in cosmetics industry. An in vivo study suggested95% ethanol extract of S. fusiforme (through gastric perfusion) couldreduce blood glucose in diabetes mice (Zhang, 2006), however theconcentration test was extremely high (350–700 mg/kg). Fucosterol,the major phytosterol in Sargassum, may have some contribution tothis anti-diabetic activity (Lee et al., 2004).

A number of reports suggested both lipophilic and hydrophilicSargassum extracts had in vitro and in vivo antioxidant activity.The in vitro antioxidant activity against DPPH radical and lipidperoxidation have been reported for different Sargassum extractssuch as 0.5% Na2CO3, enzymatic, methanol, ethyl acetate anddichloromethane extracts (Mori et al., 2003; Park et al., 2005;Shanab, 2007; Han et al., 2008). In vivo study suggested oral pre-treatment with Sargassum extracts could inhibit reduction of freeradical scavenger enzymes in acetaminophen induced lipid per-oxidation in rats and lower the CCl4 induced lipid peroxidation in

rat liver (Table 6). The antioxidant activity may also play animportant role for the protective activity against HCl–ethanolinduced gastric mucosal injury in rats (Raghavendran et al.,2004a). A number of compounds in Sargassum summarised inTables 4 and 5 such as meroterpenoids, phlorotanins and fucoi-dans may all contribute to the antioxidant activity of Sargassum

extracts.

6. Safety, traditional and modern issues

For ‘‘Hai Zao’’ ( , Sargassum), it has been clearly stated ‘‘Not tobe used with licorice ( , Glycyrrhizae Radix et Rhizoma)’’ intraditional and modern TCM documents such as ‘‘Compendium ofMateria Medica’’ ( ) and the Chinese pharmacopeia (cited inthe 1963 version). In most cases, the combination of these twomedicines is forbidden due to possible adverse effects. However thereis little reported clinical evidence and no biochemical support forthese purported adverse effects. Interestingly, ‘‘Hai Zao Yu Hu Tang’’

(Table 2), a classical Chinese prescription formallyrecorded in Summary of Surgical Medicine ( ) in 1617, haveused licorice, Sargassum and other six ingredients together. Thisprescription has been used continuously for centuries to treatdiseases such as goitre and scrofula. Similar warnings of adverseeffects with licorice are not found for another brown seaweed, Kun Bu( ), traditionally used in TCM (also named as Laminaria Thallus orEcklonia Thallus in Chinese Pharmacopeia). This traditional cautionregarding the use of licorice and Sargassum together may beexplained by opposing effects on immune function and needs to beinvestigated in more detail.

Sargassum should be generally recognised as non toxic. Theestimated LD50 of oral administration of seven Sargassum speciesincluding S. pallidum, S. fusiforme, S. thunbergii, S. horneri, S.

polycystum, S. hemiphyllum, and S. kjellmanianum for mice wasmore than 40 g/kg of body weight (Cui et al., 1997). No acutetoxicity in mice was observed after oral administration of 5 g/kgof body weight of dichloromethane, ethanol and boiling waterextracts of S. fulvellum and S. thunbergii (Kang et al., 2008). Noacute toxicity in mice was observed for intraperitoneal injectionof 500 mg/kg of body weight of hexane, sequential methanol andbutanol extracts of S. wightii (Dar et al., 2007).

Seafood may contain high level of arsenic and arsenosugar is amajor form of arsenic in Sargassum. Arsenosugar is not acutelytoxic, but there is a possibility of slight chronic toxicity (Andreweset al., 2004). Most of the arsenic in Sargassum could be removedby soaking in warm water for more than 30 min and discardingthe water extracts (Katayama and Sugawa-Katayama, 2007). Anin vitro study suggested after soaking with warm water theremaining arsenic could mostly be excreted without beingabsorbed via digestive tract (Sugawa-Katayama et al., 2010).

7. Future research for Sargassum with focus on thyroid health

The pharmacological activity of Sargassum extracts andresearch of its bioactive constituents provide scientific evidencewhich underpins the traditional therapeutical claims made forSargassum, such as treating scrofula, sore throat, cough andphlegm stasis, dropsy, furuncle (anti-microbial, antiviral andanti-inflammatory activities), hepatolienomegaly (liver protec-tion) and induce urination (possibly due to high mannitol con-tent) (Fig. 5). However, to-date one of the most important TCMclaims for Sargassum, treating thyroid related diseases (e.g.goitre), has not been sufficiently researched.

Thyroid is one of the largest endocrine glands in human body.Importantly, by producing thyroid hormones it controls how quickly

Table 6Pharmacological activities of Sargassum extracts.

Pharmacologicalactivity

Type of extract Species in vivo/

in vitroModel Administration

(in vivo)Dose Rang Active Concentration Comment Reference

Anti-

inflammatory

activity

95% Ethanol Ext. S. horneri, and

S. yezoense

in vitro Inhibition of NO and PG-E2 in RAW264.7 cells – 5–20 mg/mL

for NO 50 mg/

mL for PGE2

20 mg/mL NO Only one

concentration for

PGE2

50 mg/mL, PGE2

DCM Ext. S. fulvellum in vivo Inhibition of an inflammatory symptom of mouse ear

oedema

Topical 0.4 mg/ear 79.1%. Only one

concentration tested

Kang et al.

(2008)

DCM Ext. S. thunbergii in vivo Topical 0.4 mg/ear 72.1%.

Hexane Ext. S. wightii in vivo Anti-inflammatory against paw oedema in rats. Intraperitoneal

injection

100 mg/kg �80% for summer

collection

Only one


to compare seasonal

variation

Dar et al.

(2007)

34–59% for winter

collection

Seq. MeOH Ext.

Seq. BuOH Ext.

Anti-allergic

activity

DCM & MeOH

Ext.

S. thunbergii in vitro Inhibition of histamine release in rat peritoneal mast cells – 100 mg/mL 49.8% inhbition Only one


Lee et al.

(2006)

MeOH Ext. S. hemiphy-

llum

in vitro Inhibited histamine and b-hexosaminidase release from

rat peritoneal mast cells. Inhibited interleukin (IL)-8 and

TNF-a release

– 10–1000 mg/

mL

active on the high


– Na et al.

(2005)

from HMC-1 cells, inhibited the increase of NF-kB

protein levels, transcription factor of TNF-a from 293T

cells.

in vivo Inhibition of passive cutaneous anaphylaxis reaction in

mice induced by IgE

Oral 10–1000 mg/

mL

100 and 1000

mg/mL

(1) Acetone/

DCM and

MeOH Ext.;

(2) Hexane Fr.;

(3) 85%

MeOH Fr.

(4) BuOH Fr.

(5) H2O Fr.

S. thunbergii in vitro Inhibited the histamine release from rat peritoneal mast

cells

– 100 mg/mL (1) Inhibited

histamine, 49.85%; IL-

4, 6, 8. (4) Inhibited

histamine, 59.62%; IL-

4, 6, 8

Only one


Na et al.

(2004)

Reduced IL-8 in the human mast cell line

Antimicrobial EtOAc Fr. of

MeOH Ext.

S. hystrix and

S. filipendula

in vitro Staphylococcus aureus, Bacillus subtilis, Streptococcus

agalactiae, Escherichia coli, Pseudomonas aeruginosa,

Klebsiella pneumoniae, Shigella flexneri, Candida albicans,

Saccharomyces cerevisae, Aspergillus niger, and

Trichophyton mentagrophytes

– – 3.13–6.25 mg/mL – Morales et al.

(2006)

EtOAc Fr. of 95%

EtOH Ext.

S.

kjelimanianum

in vitro Antibacterial against Staphylococcus aurens – 32 mg/mL 32 mg/mL Only one


Xu et al.

(2002a)

MeOH:H2O:HCl

(1:10:0.15) Ext

S. filipendula in vitro Antifungal against Aspergillus niger, A. flavus, A.

parasiticum, Penicillum spp., Fusarium oxysporum, Candida

albicans, C. rugosa.

– 22.5�200mg/

mL

200mg/mL Very high


Martinez-

Lozano et al.

(2000)

Benzene Ext./

Seq. CHCl3 Ext./

MeOH Ext.

S. wightii in vitro Staphylococcus aureus, Escherichia coli, Proteus vulgaris,

Psedomonas aeruginosa, Salmonella paratyphi A., S. typhi, S.

typhimurium

– 30ug of

extract on

6 mm discs

CHCl3 extract

exhibited the greatest

antibacterial activity

– Sastry and Rao

(1994)

Antiviral activity MeOH Ext. S. hemiphyllum in vitro Promote production of interferon b (IFN-b) in MG-63 cells – – 11.25 for IFN-b relative

productivity

Concentration used

not stated

Nakano et al.

(1997)

Active Fr. of

above

in vivo Mice infected with Aujeszky’s disease virus Not stated 6.3–100 mg/

kg

100 mg/mL, 7 out of 10

mice survived

Antiviral activity by

modulating host

immunodefense

system

Nakano and

Kamei (2005)

Water Ext. S.vulgare in vitro Antiviral in HeLa cells co-cultured with Human T-cell

Lymphotropic Virus Type 1 (HTLV-1) infected T-cell line

– 0–5% 78.8% syncytium

inhibition at 5%

concentration

– Romanos et al.

(2002)

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MeOH Ext. S. connfusum

and S.

hemiphyllum

in vitro Inhibition of HIV-1 (a) integrase, (b) reverse transcriptase. – a: 200 mg/mL

b: 10, 25, 100

mg/mL

a: 200 mg/mL

b: 100 mg/mL

EtOAc Fr. most potent

inhibitory activity,

indicate activity not

from polysaccharides

Ahn et al.

(2002)

70% EtOH Ext. S. wightii in vitro Reduce plaques formed by vaccinia virus in chick embryo

fibroblast cell culture

– – CC50¼132 mg/mL

EC50¼38 mg/mL

Selective index¼3.44

– Premanathan

et al. (1994)

Antiplasmodial

activity

DCM Fr. of MeOH

and DCM Ext.

S. heterophy-

llum

in vitro Antiplasmodial activity against Plasmodium falciparum – – IC50¼2.8 mg/mL – Lategan et al.

(2009)

Anticancer Water Ext. S. oligocystum in vitro K562 and Daudi human cancer cell lines – 0–500 mg/mL about 60% inhibition at

500 mg/mL

– Zandi et al.

(2010)

Hexane Fr.of

MeOH Ext.

S. swartzii in vitro Cytotoxicity against HT-29, Caco-2, T47D, MDA-MB468

and NIH 3T3 cell lines

– – IC50o100 mg/mL for

Caco-2 cells and T47D

cells

Apoptosis observed Khanavi et al.

(2010)

Hot water Ext. S. horneri in vitro Meth-A cell line – 5–25 mg/mL 25 mg/mL – Matsuda et al.

(2005)

in vivo Meth-A tumor bearing BALB/c female mice Oral 0.01% or

0.05%�105

mL/mouse

0.05%�105

mL/mouse

Intraperitoneal

injection

0.1 and 0.5

mg/mouse

0.1 mg/mouse

Hot water Ext. S. fulvellum in vivo Anticancer against the growth of subcutaneously

implanted sarcoma-180 solid tumor in mice

Intraperitoneal

injection

10 mg/kg 10 mg/kg Only one


Yamamoto

et al. (1974)

Water Ext. S. kjellmania-

num

in vivo Anticancer on the growth of sarcoma-180 cells

subcutaneously implanted into mice

Intraperitoneal

injection

50, 100 mg/kg 93.7% for 100

mg/mL

– Yamamoto

et al. (1981)

Liver protection EtOH Ext. S. polycystum in vivo Protection against acetaminophen induced toxic hepatitis

in rats

Oral 200 mg/kg Inhibition of TNF-a

Protected the liver

structural integrity

Only one


Raghavendran

et al. (2006)

EtOH Ext. S. polycystum in vivo Protection against acetaminophen induced hepatic

oxidative stress in rats

Oral 200 mg/kg Reduced biochemical

changes in the serum

and liver tissue

Only one


Raghavendran

et al. (2004b)

Water Ext. S.

henslowianum

and S.

siliquastrum

in vivo Reduced CCl4-induced acute elevation of serum glutamic

pyruvic transaminase (GPT) and glutamic oxaloacetic

transminase (GOT) in rats.

Oral 150, 300,

600 mg/kg

150, 300, 600 mg/kg – Wong et al.

(2000)

Bone protection Water Ext. S. horneri in vitro Rat femoral-diaphyseal and –metaphyseal tissue – 25 mg/mL Stimulate bone

formation

Only one


Uchiyama

et al. (2004)

Mouse marrow cells 1.0 mg/mL Suppress osteoclastic

bone resorption

Only one


Water Ext. S. horneri in vivo Reduce bone loss in streptozotocin-Diabetic rats – 10 mg/100 g Prevent effect on bone

loss

Only one


Uchiyama and

Yamaguchi

(2003)

Water Ext. S. horneri in vitro Rat femoral-diaphyseal and –metaphyseal tissue – 10, 25, 50

mg/mL

Inhibitory effect on

bone resorption

– Uchiyama and

Yamaguchi

(2002b)

Water Ext. S.horneri in vivo In femoral-diaphyseal and –metaphyseal tissues of Rats Oral 2.5, 5, 10

mg/100 g

10 mg/100 g – Uchiyama and

Yamaguchi

(2002a)

Water Ext. S.horneri in vivo Bone calcification content and bone alkaline phosphatise

activity in rat

Oral 5%, 1 mL/

100 g

5%, 1 mL/100 g Only one


Yamaguchi

et al. (2001)

in vitro Enhance alkaline phosphatise in rat femoral-metaphyseal

tissues

25, 50 mg/mL 50 mg/mL

Skin-whitening

agent

Hexane Fr. of

EtOH Ext.

S. polycystum in vitro B16F10 murine melanoma cells – 100, 250 and

500 mg/mL

15.13, 28.71 and

39.93% inhibition

- Chan et al.

(2011)Test for inhibition on melanin production.

Water Ext. (20oC) S. silquastrum in vivo Zebrafish embryo, inhibited both tyrosinase activity – 100 mg/mL 50% inhibition for both in vivo model need

further development

Cha et al.

(2011)and total melanin contents

in vitro Tyrosinase inhibitory activity against mushroom

tyrosinase

IC50¼19.85 mg/mL

L.Liu

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61

96

13


Pharmacologicalactivity

Type of extract Species in vivo/

in vitroModel Administration

(in vivo)Dose Rang Active Concentration Comment Reference

Melanin synthesis inhibitory activity on B-16 cell line IC50¼72.68 mg/mL

Treat Alzheimer’s

disease

MeOH Ext. S.

macrocarpum

in vitro Neurite outgrowth promoting activity in a rat adrenal

medulla pheochromocytoma cell line, PC12D

– 1.5–200 mg/

mL

3–12.5 mg/mL Cytotoxicity observed

at greater than 25 mg/

mL

Kamei and

Sagara (2002)

Hypoglycemic

effect

95% EtOH S. fusiforme in vivo Reduce blood glucose in diabetes mice Gastric

perfusion

350 mg/kg reduce from 28 to

23 mmol/L

– Zhang (2006)

700 mg/kg reduce from 26 to

18 mmol/L

Gastric protection Hot water Ext. S. polycystum in vivo Induced gastric mucosal injury in rats Oral 100 mg/kg Maintain the volume/

acidity of gastric juice

and improve the

gastric mucosa

antioxidant

Only one


Raghavendran

et al. (2004a)

Antioxidant Acetone and

DCM Ext.

S.horneri in vitro Intracellular reactive oxygen species (ROS) scavenging

effect, NO reduction, and increase GSH (glutathione) in

mouse macrophage Raw 264.7 cells.

– 20 mg/mL for

ROS, 50 mg/

mL for NO

and GSH

47%-ROS Only one


Kim et al.

(2008b)47.5%-NO

11%-GSH

Seq. MeOH Ext.

of above

3%-ROS

63.5%-NO

23%-GSH

0.5% Na2CO3 Ext. S. fusiforme in vitro DPPH radical scavenging activity – 0.3–10 mg/mL About 93% at 10

mg/mL

– Han et al.

(2008)

DCM Ext. S. dentifolium in vitro DPPH radical scavenging and inhibition of lipid

peroxidation (LPO)

– 10, 50,

100 mg/mL-

DPPH

86%-DPPH – Shanab (2007)

83%-LPO

100 mg/mL-DCM

100 mg/mL-EtOH

70% EtOH Ext. 0.25, 0.5,

1 mg/mL-LPO

82%-DPPH

69%-LPO

Water Ext. and

EtOH Ext.

S. polycystum in vivo Inhibit the reduction of free radical scavenger enzymes in

acetaminophen induced lipid peroxidation in rats

Oral

pretreatment

100 and

200 mg/kg

active for both

concentration

– Raghavendran

et al. (2005)

Enzymatic Ext. S. thunbergii in vitro Hydroxyl, DPPH, alkyl radicals scavenging activity and

DNA damage protective activity.

– 5–25 mg/mL Significant activity

seen at 25 mg/mL

– Park et al.

(2005)

Enzymatic Ext. S. horneri in vitro Hydroxyl, DPPH, alkyl radicals scavenging activity – 5–25 mg/mL Significant activity

seen at 25 mg/mL

Spin-trapping

electron spin

resonance

spectrophotometer

method developed

Park et al.

(2004)

MeOH Ext. S. micracanth- in vitro Inhibition of lipid peroxidation (LPO) in rat liver

homogenates

– – IC50¼0.7, 0.7, 0.37 mg/

mL-LPO

– Mori et al.

(2003)

CHCl3/ um DPPH radical scavenging activity IC50¼34, 37, 11 mg/

mL-DPPHMeOH Ext.

EtOAc Ext.

MeOH Ext. in vivo Lower lipid peroxidation in rat liver Oral 120–1200

mg/kg

14.7% inhibition for

1200 mg/kg

CHCl3 Ext./Seq.

EtOAc Ext. /Seq.

acetone Ext. /Seq.

MeOH Ext.

S. thunbergii in vitro DPPH radical scavenging activity – not stated

clearly

10% (CHCl3) Concentration tested

not stated

Yan et al.

(1999)o10%(EtOAc)

10% (Acetone)

30% (MeOH)

L.Liu

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Traditional ChineseMedicine (TCM)

Sargassum

Hai

Zao

Pharmacological activity

AnticancerAnti-inflammatoryAntibacterial Antiviral activities

Anticoagulant Antimelanogenic Hepatoprotective Neuroprotective

Bioactive Phytochemicals

Polyunsaturated fatty acidsMeroterpenoids PhlorotaninsFucoidans

FucoxanthinPhytosterols

TreatGoitreScrofulaEdema

Therapeutical effects in TCM

Soften Hard Lumps Dispel NodesEliminate Phlegm Induce Urination.

FutureResearch Immunomodulators

Treat Thyroid Diseases

Hashimoto’s thyroiditis Graves' disease

Fig. 5. Research of Sargassum past, present and future.


the body uses energy, synthesises proteins, and controls howsensitive the body is to other hormones (Michelangeli et al., 2000).Thyroid disease, is a highly prevalent disease, effecting one in sevenpeople around the world. Goitre, referred to a disease with enlarge-ment of thyroid, can associate with both hypothyroidism andhyperthyroidism (Abraham-Nordling et al., 2005; Babademezet al., 2010). The iodine in Sargassum may help to control or treatendemic goitre, a type of goitre that is associated with dietary iodinedeficiency. TCM claims Sargassum can resolve ‘‘hard mass’’ such asgoitre. The goitre treated by Sargassum in TCM may be not limited toendemic goitre, but little research has been done in this area.

Elevated level of thyroid peroxidise antibody (TPOAb) and thyr-oglobulin antibody (TgAb) can often be observed in autoimmunedisorders such as Hashimoto’s thyroiditis and Graves’ disease(Shivaraj et al., 2009). The high levels of these antibodies ofteninvolved with chronic inflammation of the thyroid gland that,eventually, causes the gland to become underactive and sometimesleads to thyroid cancer. Besides iodine, bioactive phytochemicals inSargassum may play a more important role in treating thyroiddiseases. Resent research suggested Sargassum could reduce thelevels of TPOAb and TgAb in rats (Song et al., 2011), which couldbe attributed to the immunomodulatory activity such as anti-inflammatory and anti-allergic activities of Sargassum. The pathogen-esis of autoimmune disorders of thyroid such as Hashimoto’sthyroiditis and Graves’ disease are still not clear. The antimicrobialand antiviral activities may also contribute to the therapeutic effectsof Sargassum on thyroid related diseases. Sargassum has a consider-able potential for improving thyroid health, but further biochemicaland clinical research are required to understand the function ofSargassum for treating thyroid diseases. At this stage developingpreventive uses seem to be the more appropriate strategy.

8. Conclusion

Sargassum is a rich source of bioactive compounds with widerange of health benefits. However, the difference between the

bioactive compounds of Sargassum species has not been studied.Although only two species of Sargassum, S. pallidum andS. fusiforme have been listed in Chinese Pharmacopeia (2010version), other species such as S. fulvellum, S. henslowianum,S. thunbergii and S. horneri may be used for similar medicaltreatments. A systemic phytochemical study of these Sargassum

species could help to determine the biological activity of eachspecies for medicinal uses and assist the taxonomic study ofthis genus.

A large number of studies suggested that Sargassum has anti-inflammatory, anticancer, antimicrobial, antiviral, liver protectiveand antioxidant activity. This pharmacological activity and iden-tified bioactive compounds provides solid scientific evidence forsome of the traditional therapeutical claims of Sargassum. How-ever in many studies there is a general lack of proper phyto-chemical characterisation of the extracts used. Future researchwill need to incorporate such a profiling. As discussed above,priority should be given to investigating Sargassum’s potential forpreventing and treating thyroid diseases.

Acknowledgements

S. A. Dworjanyn and L. Liu were supported by the AustralianCentre for International Agricultural Research.

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Liu-etal Seaweeds JEP142-2012

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