Review Article Ethnobotanical, Phytochemical, Pharmacological, and Toxicological Aspects of...

Review ArticleEthnobotanical Phytochemical Pharmacological andToxicological Aspects of Persicaria hydropiper (L) Delarbre

A K M Moyeenul Huq1 Jamia Azdina Jamal1 and Johnson Stanslas2

1 Centre for Drug and Herbal Research Faculty of Pharmacy Universiti Kebangsaan Malaysia Jalan Raja Muda Abdul Aziz50300 Kuala Lumpur Malaysia

2 Pharmacotherapeutics Unit Department of Medicine Faculty of Medicine and Health Sciences Universiti Putra Malaysia43400 Serdang Selangor Darul Ehsan Malaysia

Correspondence should be addressed to Jamia Azdina Jamal jamiajamalgmailcom

Received 6 February 2014 Accepted 25 March 2014 Published 16 April 2014

Academic Editor Man Hee Rhee

Copyright copy 2014 A K M Moyeenul Huq et alThis is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in anymedium provided the originalwork is properly cited

Persicaria hydropiper (L) Delarbre belonging to Polygonaceae family is a common weed found in most of the temperate countriesincluding Bangladesh China Malaysia and Japan The plant is also referred to as ldquomarsh pepperrdquo or ldquosmart weedrdquo It appearsto be a useful herb with evidence-based medicinal properties The present work addresses the botanical description traditionaluses phytochemistry pharmacology and toxicology of P hydropiper All plant parts have been commonly used in the traditionalsystems of medicines Flavonoids are the major group of phytochemical components followed by drimane-type sesquiterpenes andsesquiterpenoids as well as phenylpropanoids Different extracts and plant parts showed remarkable pharmacological activitiesincluding antioxidant antibacterial antifungal antihelminth antifeedant cytotoxicity anti-inflammatory antinociceptiveoestrogenicity antifertility antiadipogenicity and neuroprotection Mutagenicity and acute and subchronic toxicities of the plantwere also reported P hydropiper has tremendous medicinal properties that could further be investigated for the development ofevidence-based herbal products

1 Plant BotanicalDescription and Distribution

Persicaria hydropiper (L) Delarbre belongs to the family ofPolygonaceae The synonyms for this species include Persi-caria hydropiper (L) Spach P hydropiper (L) Opiz P hyd-ropiper (L) H Gross Polygonum hydropiper L and P hydro-piper var projectum Stanford [1ndash4]

The species is com-monly known as marsh-pepper smartweed marsh-pepperknotweed smartweed or water pepper [5ndash7] and is alsocalled la liao in China [8] bishkatali or pakarmul in Bangla-desh [9] and daun senahun in Malaysia [10]

Based on the information stated in the Flora of NorthAmerica and Flora of China [4 8] P hydropiper is an annualplant of 40ndash70 cm tall Briefly it has a decumbent to asce-nding or erect branched and glabrous stem The leavesare lanceolate or elliptic-lanceolate (4ndash10 times 04ndash25 cm) andglabrous with petiole (01ndash08 cm) cuneate base acute toacuminate apex ciliated margin and sessile attachment withstipule The terminal and axillary inflorescences (03ndash180

times 05ndash09 cm) are either erect or nodding with glabrouspeduncle (01ndash05 cm) ascending pedicels and 3ndash5 flowersThe flowers have greenish proximal and white or pink distalperianth obovate tepals 6ndash8 stamens and 2-3 styles

P hydropiper is distributed worldwide and found nativein temperate and tropical Asia including Western AsiaCaucasus Siberia Middle Asia Russian Far East ChinaEastern Asia Indian Subcontinent Indo-China andMalesiaEurope region such as Northern EuropeMiddle Europe EastEurope Southeastern Europe and Southwestern EuropeNorthern Africa and Australia [11]The plant generally growsin wet areas at watersides and in marshes [12] and is usuallypredominant in agricultural fields [13] It is also commonlydistributed to highland sites with highly organic moist orsilty areas [14]

2 Traditional Uses

Persicaria hydropiper has a strong peppery taste and is com-monly used as a hot-tasting spice food flavor and garnish

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2014 Article ID 782830 11 pageshttpdxdoiorg1011552014782830

2 Evidence-Based Complementary and Alternative Medicine

for a variety of traditional dishes [15ndash17]The Japanese peopleuse the young shoot as spice and garnish with raw fish suchas ldquosashimirdquo for its pungent taste [18] while the water orethanol leaf extract served as a food additive to preservepickles dressing and cooked foods [19] In Southeast Asiathe Chinese and Malays use the leaves in traditional laksadishes [16]

Most importantly P hydropiper also has a wide range oftraditional uses for medicinal purposes In Europe the planthas been used as diuretic and emmenagogue [20] and toregulate menstrual irregularities [21] In addition decoctionof thewhole plant either alone ormixedwith othermedicinalplants is also given for diarrhea dyspepsia itching skinexcessive menstrual bleeding and hemorrhoids [22] Theleaves and seeds are used in a folk medicine against cancer[23]The Romanian people in Oltenia utilized infusion of theaerial part as astringent and cicatrising as well as for gastricpulmonary problems and uterine hemorrhages [24]The useof bruised leaves and seeds as vesicants has also been reported[25]

In India theMishingwomen inAssam take the dried rootpowder of P hydropiper for termination of pregnancy andit may lead to permanent sterility if taken continuously formore than a year [26 27] Leaf rsquos juice is consumed for uterinedisorders [28] In Arunachal Pradesh the whole plant extractand ground plant paste are used as fish poisons [28 29]whereas the leaf infusion is used to relieve colic pain [30]Theplant has also been utilized as natural dyes [31]

In Bangladesh the Garo tribe uses the leaf juice formenstrual pain the leaf paste to stop bleeding and the wholeplant as pesticide for stored grains [32] Another tribe ofTripura uses the mixture of crushed P hydropiper leaf withblack pepper for headache [33] In a district of Sylhet thecrushed plant helps to arrest hemorrhage and in Rema-Kalenga the leaves are used for stomach pain [34] The leafjuice has been given for treating many health problems likeheadache pain toothache liver enlargement gastric ulcerdysentery loss of appetite and dysmenorrhea while the rootsare used as stimulant and their juice is applied towounds skindiseases and painful carbuncles [35]

In Vietnam the stems and leaves are taken for snake-biteand as diuretic and anthelmintic [12] In China the plant isconsumed to prevent ovulation and cease pregnancy [36]while the root is used as stimulant diuretic carminativetonic and anthelmintic [37]

This plant has been found to be toxic to pigs and sheep[38]

3 Phytochemical Constituents

P hydropiper has been reported to contain mainly flavonoidssesquiterpenes sesquiterpenoids and phenylpropanoids(Table 1)

Various extracts and fractions ofP hydropiperwhole plantand herbs were found to contain flavonoids such as (+)-catechin (minus)-epicatechin hyperin isoquercitrin (Figure 1)isorhamnetin (Figure 1) kaempferol quercetin (Figure 1)quercitrin rhamnazin and rutin [39ndash41] drimane-typedsesquiterpenes such as 3-120573-angeloyloxy-7-epifutronolide

7-ketoisodrimenin changweikangic acid A dendocarbin L(+)-fuegin futronolide polygonumate and (+)-winterin[42] phenylpropanoid esters including hydropiperosides Aand B (Figure 1) and vanicosides A (Figure 1) B and E [43]as well as phenolic acids such as caffeic acid chlorogenic acidand 120588-coumaric acid [41]

Methanol (80ndash100) extract of the leaves had mainlyflavonoids including apigenin-7-O-glucoside galloyl kaemp-ferol-3-O-glucoside galloyl quercetin-3-O-glucoside gall-oyl quercetin-3-O-rhamnoside galloyl quercitrin (Figure 1)isoquercitrin isoquercitrin-3-glucoside isorhamnetin isor-hamnetin-37-disulphate (Figure 1) kaempferol rutinosidekaempferol-3-O-glucoside percicarinpersicarin quercitrinquercetin (Figure 1) quercetin-3-O-glucoside quercetin-3-O-120573-D-glucuronide quercetin-3-O-rhamnoside (Figure 1)quercetin-3-sulphate rhamnazin rhamnazin-3-sulphaterhamnetin scutillarein tamarixetin-3-O-120573-glucoside-7-sul-phate 31015840-methylquercetin 6-hydroxyluteolin 6-hydroxy-luteolin-7-O-120573-D-glucopyranoside 6-hydroxyapigenin and741015840-dimethylquercetin (Figure 1) [16 17 44ndash46] pheny-lpropanoids such as hydropiperosides and vanicosides A Band D and 35-dihydroxy-4-methoxybenzoic acid (Figure 1)[17] Additionally the leaf diethyl ether extract was foundto have sesquiterpenes and sesquiterpenoids such as con-fertifolin (Figure 1) drimenol (+)-fuegin isodrimeninolisopolygodial isopolygonal polygodial (Figure 1) polygodialacetal polygonal polygonic acid polygonone valdiviolidewarburganal (Figure 1) and 11-ethoxycinnamolide [18 47]whereas the essential oil had acetic acid confertifolin diethy-leneglycol monoacetate ethyl benzene ethyl propionate andn-propyl acetate [48]

The methanol extract of stems and leaves was reportedto contain hydropiperosides A and B and vanicosides AB and E [43] while the petroleum extract of top parthad polygodial [49] and the methanol extract of roots hadanthraquinone ellagic acid 331015840-di-O-methyl ether gallicacid hydropiperosides and polygonolide (Figure 1) [50 51]Several sesquiterpenes and sesquiterpenoids such as con-fertifolin drimenol isodrimeninol isopolygodial polygo-dial polygonal and warburganal have been isolated fromdiethyl ether extract of the seeds [18 52] (+)-catechin (+)-epicatechin and (+)-epicatechin-3-O-gallate were producedby the callus and suspension-cultured cells of P hydropiper[53] whereas polygodial was detected in the shoot cultures[54]

4 Pharmacological Properties

Several reports on pharmacological properties of P hydro-piper are available to support the ethnomedicinal uses ofthe plant including antioxidant antibacterial antifungalantihelminth antifeedant cytotoxicity anti-inflammatoryantinociceptive oestrogenicity anti-fertility anti-adipogeni-city anticholinesterase and neuroprotection Toxicologicaleffects of P hydropiper are also described

41 Antioxidant Activity Flavonoids are powerful antioxi-dants that can protect the human body from free radicals[55] Isoquercitrin and 7 41015840-dimethylquercetin isolated from

Evidence-Based Complementary and Alternative Medicine 3

Table 1 List of chemical constituents isolated from Persicaria hydropiper

Class of compound Name of compound Plant part Type of extract References

Flavonoids

Apigenin-7-O-glucoside Leaves MeOH [17](+)-Catechin Whole plant MeOH (80) [40]

Herbs MeOH fraction [41]Callus and suspension-cultured cells Acetone [53]

(minus)-Epicatechin Whole plant MeOH (80) [40]Herbs MeOH fraction [41]

Callus and suspension-cultured cells Acetone [53](minus)-Epicatechin-3-O-gallate Callus and suspension-cultured cells Acetone [53]

Galloyl quercitrin Leaves MeOH (80) [16]Galloyl quercetin-3-O-glucoside Leaves MeOH [17]Galloyl kaempferol-3-O-glucoside Leaves MeOH [17]

MeOH (80) [16]Galloyl quercetin-3-O-rhamnoside Leaves MeOH [17]

Hyperin Whole plant MeOH (80) [40]Isoquercitrin Whole plant MeOH (80) [40]

Leaves MeOH [44]Isoquercitrin 3-glucoside Leaves MeOH [45]

Isorhamnetin Whole plant MeOH (80) [40]Herbs EtOAc fraction [39]Leaves MeOH [45]

Isorhamnetin 37-disulphate Leaves MeOH [46]Kaempferol Whole plant MeOH (80) [40]

Herbs EtOAc fraction [39]MeOH fraction [41]

Kaempferol rutinoside Leaves MeOH [17]Kaempferol-3-O-glucoside Leaves MeOH [17]

MeOH (80) [16]Percicarinpersicarin Leaves MeOH [45]

Quercitrin Whole plant MeOH (80) [40]Leaves MeOH (80) [16]

Quercetin Whole plant MeOH (80) [40]Herbs EtOAc fraction [39]

MeOH fraction [41]Leaves MeOH [17 44 45]

MeOH (80) [16]Quercetin 3-sulphate Leaves MeOH [46]

Quercetin-3-O-glucoside Leaves MeOH [17]Quercetin-3-O-rhamnoside Leaves MeOH [17]

Quercetin-3-O-120573-D-glucuronide Leaves MeOH (80) [16]Rhamnazin Herbs EtOAc [39]

Leaves MeOH [45]Rhamnazin-3-sulphate Leaves MeOH [45]

Rhamnetin Leaves MeOH [17]Rutin Whole plant MeOH (80) [40]

Herbs MeOH fraction [41]Scutellarein Leaves MeOH (80) [16]

Tamarixetin 3-O-120573-glucoside-7-sulphate Leaves MeOH [46]31015840-Methylquercetin Leaves MeOH [44]6-Hydroxyluteolin Leaves MeOH (80) [16]

6-Hydroxyluteolin-7-O-120573-D-glucopyranoside Leaves MeOH (80) [16]6-Hydroxyapigenin Leaves MeOH (80) [16]

741015840-Dimethylquercetin Leaves MeOH [44]


Table 1 Continued


Phenylpropanoids

Hydropiperoides Roots MeOH [50]Leaves MeOH [17]

Hydropiperoides A Stems and leaves MeOH [43]Hydropiperoides B Stems and leaves MeOH [43]

Vanicoside A Stems and leaves MeOH [43]Leaves MeOH [17]

Vanicoside B Stems and leaves MeOH [43]Leaves MeOH [17]

Vanicoside D Leaves MeOH [17]Vanicoside E Stems and leaves MeOH [43]

Sesquiterpenes and sesquiterpenoids

Changweikangic acid A Whole plant MeOH [42]Confertifolin Leaves Diethyl ether [18]

Essential oil [48]Seeds Diethyl ether [18 52]

Dendocarbin L Whole plant MeOH [42]Drimenol Leaves Diethyl ether [18]

Seeds Diethyl ether [18](+)-Fuegin Whole plant MeOH [42]

Leaves Diethyl ether [47]Futronolide Whole plant MeOH [42]

Isodrimeninol Leaves Diethyl ether [18]Seeds Diethyl ether [18 52]

Isopolygodial Leaves Diethyl ether [18]Seeds Diethyl ether [18 52]

Isopolygonal Leaves Diethyl ether [47]Polygodial Top part Petroleum [49]

Leaves Diethyl ether [18]Seeds Diethyl ether [18 52]

Shoot cultures mdash [54]Polygodial acetal Leaves Diethyl ether [47]Polygonumate Whole plant MeOH [42]Polygonal Leaves Diethyl ether [18]

Seeds Diethyl ether [18 52]Polygonic acid Leaves Diethyl ether [47]Polygonone Leaves Diethyl ether [47]Valdiviolide Leaves Diethyl ether [47]Warburganal Leaves Diethyl ether [18]

Seeds Diethyl ether [18](+)-Winterin Whole plant MeOH [42]

3-120573-Angeloyloxy-7-epifutronolide Whole plant MeOH [42]7-Ketoisodrimenin Whole plant MeOH [42]

11-Ethoxycinnamolide Leaves Diethyl ether [47]

Others

Acetic acid Leaves Essential oil [48]Anthraquinone Roots MeOH [50]Caffeic acid Herbs MeOH fraction [41]

Chlorogenic acid Herbs MeOH fraction [41]120588-Coumaric acid Herbs MeOH fraction [41]

Diethylene glycol monoacetate Leaves Essential oil [48]Ellagic acid 331015840-di-O-methyl ether Roots MeOH [50]

Ethyl benzene Leaves Essential oil [48]Ethyl propionate (propionic acid ethyl ester) Leaves Essential oil [48]

Gallic acid Roots MeOH [50]35-Dihydroxy-4-methoxybenzoic acid Leaves MeOH [17]

Polygonolide Roots MeOH [51]n-Propyl acetate Leaves Essential oil [48]


O

OH

OH

OIsorhamnetin

OO

OO SO O

SO

O

O

OQuercetin

O

O

O

O

O

O

O

OO

O

O

OO

Hydropiperoside B

O

O HConfertifolin

CHO

CHO

H

Polygodial

O

OO

O

Isoquercitrin

O

OO

O C

OH

O

O

O

Galloyl quercitrin

O

O

O OOH

O

O

OPolygonolide

O

O

O

O

O

O

O

O

O

O

O

O

O

Vanicoside A

H

H

H

OO

Warburganal

OH

OH

OH

OHOH

OHOH

OHOH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OHOH OH

OH

OHOH

OH

OH

OH

OH

OHOH

HO

HO

HOHO

HO

HO

HO HOHO

HO

HO

HO

HO

HO

HO

HO

OCH3

H3CO

CH3

CH3

CH3

CH3

CH2OH

H3C

H3C

CH3

CH3

H3CO

H3C

H3C

CH3

CH3

CH3

CH3

OCH3

H3CO

OCH3

OCH3

OCH3

H3CO

H3CO

Isorhamnetin-37-disulphate

74998400-Dimethylquercetin

Quercetin-3-O-rhamnoside

35-Dihydroxy-4-methoxybenzoic acid

Ominus

minus

O

Figure 1 Bioactive phenolics and sesquiterpenoids of Persicaria hydropiper


the methanol extract of P hydropiper leaves were foundto inhibit lipid peroxidation using ferric thiocyanate (FTC)method with ID

50

of 06 and 15 ppm respectively [44] Yagiet al [46] also studied the antioxidant activity of quercetin-3-sulphate isorhamnetin-37-disulphate and tamarixetin-3-glucoside-7-sulphate isolated from the methanol leafextract Amongst the sulphated flavonoids isorhamnetin-37-disulphate gave the strongest inhibition against lipidperoxidation even compared to 120572-tocopherol and quercetinand the formation of superoxide anion and xanthine oxidasecompared to quercetin

Peng et al [16] investigated the antioxidant properties of10 flavonoids isolated from the leaves of P hydropiper that isquercitrin kaempferol-3-glucoside 6-hydroxyapigenin gal-loyl kaempferol-3-glucoside scutillarein 6-hydroxyluteolin6-hydroxyluteolin 7-O-120573-D-glucopyranoside quercetin 3-O-120573-D-glucuronide galloyl quercitrin and quercetin show-ing Trolox equivalent antioxidant capacity (TEAC) valuesof 139ndash614 against 221015840-azinobis(3-ethyl-benzothiazoline-6-sulphonic acid (ABTS) radicals Galloyl quercitrin was themost powerful antioxidant found in the study (TEAC = 614)compared to quercitrin (TEAC = 346) and its aglyconequercetin (TEAC = 465)

Hydropiperoides B and vanicoside A isolated from the Phydropiper methanol leaf extract demonstrated antioxidantactivity in 11-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging assay with half maximal scavenging concen-tration (SC

50

) values of 234 and 267 120583gmL respectivelycompared to ascorbic acid (SC

50

220120583gmL) [43] NoorHashim et al [17] also reported the antioxidant activity ofethyl acetate fraction of methanol leaf extract against DPPHfree radicals with IC

50

value of 1330 120583gmL whereby the35-dihydroxy-4-methoxybenzoic acid (IC

50

808120583gmL)quercetin (IC

50

1114 120583gmL) and quercetin-3-O-rhamnoside(IC50

1846 120583gmL) were found to bemost active as comparedto vitamin C (IC

50

680120583gmL)

42 Antibacterial Activity Confertifolin isolated from theleaf essential oil of P hydropiper showed stronggood anti-bacterial activity against Enterococcus faecalis (MIC3125 120583gmL) as compared to a positive standard strepto-mycin (MIC 25 120583gmL) but did not inhibit the growth ofBacillus subtilis Erwinia sp Escherichia coli Klebsiella pneu-moniae Pseudomonas aeruginosa Staphylococcus aureus andS epidermidis [48]On the other hand Kubo et al [56] reve-aled that polygodial had moderate bactericidal action againstBacillus subtilis (minimum bactericidal concentrationMBC 100 120583gmL) Staphylococcus aureus (MBC 100 120583gmL)Escherichia coli (MBC 100 120583gmL) and Salmonella cholera-esuis (MBC 50 120583gmL)

43 Antifungal Activity Confertifolin isolated from the leafessential oil was also found to have potent antifungal activityagainst Epidermophyton floccosum Curvularia lunata andScopulariopsis sp (MIC 781120583gmL) and moderate activ-ity against Aspergillus niger Botrytis cinerea Magnaporthegrisea Trichophyton mentagrophytes Trichophyton rubrum(MTCC 296 and clinical isolate) andTrichophyton simii (MIC

1662ndash125 120583gmL) as compared to fluconazole (MIC lt 125ndash100 120583gmL) and ketoconazole (MIC lt 125 120583gmL) [48]

Polygodial was also reported to inhibit Candida albicansC utilis C krusei Cryptococcus neoformans Saccharomycescerevisiae Epidermophyton floccosum Trichophyton menta-grophytes T rubrum and Penicillium marneffei [57 58] Itshowed potent fungicidal activity against C albicans [58] Inanother studies polygodial isolated from Warburgia speciesand P hydropiper showed fungicidal activity against S cere-visiae [59 60] via several mechanisms such as decreasingcytoplasmic and mitochondrial glutathione and increasingproduction of reactive oxygen species [61] and inhibition ofmitochondrial ATPase [62 63] Later Fujita and Kubo [64]revealed that polygodial a nonionic surfactant denaturedthe lipid-protein conformation of the cell membrane andinteracted with L-cysteine containing cytoplasmic materialssuch as glutathione

44 Anthelmintic Activity Methanol (99) extract of P hyd-ropiper aerial plant part (50mgmL) displayed anthelminticactivity against adult earthworms Pheretima posthuma invitro with time of paralysis and death of 1244 and 1819minrespectively compared to the positive standard piperazinecitrate (10mgmL time of paralysis = 2400min time ofdeath = 3800min) [65]

45 Antifeedant Activity Hot water extract of P hydropiperleaves (10wv) was significantly effective against the beanaphids Aphis craccivora with 876ndash945 mortality (119875 lt001) 7 days after the application of spray at 227 Lha [14]

Warburganal was previously reported to have strongantifeedant activity against African armyworms Spodopteraexempta [66] and aphids [67] Polygodial was found to beactive antifeedant against a variety of aphids (Aphis cra-ccivora Myzus persicae and Rhopalosiphum padi) Africanor Egyptian cotton leafworm (Spodoptera littoralis) andwhiteflies (Bemisia tabaci) [67ndash70]

46 Cytotoxic Activity Various fractions ofP hydropiper herband root methanol extracts were tested for antiproliferativeactivity against cervical epithelial adenocarcinoma (HeLa)skin epidermoid carcinoma (A431) and breast epithelial ade-nocarcinoma (MCF7) cells only hexane fraction of the rootmethanol extract (30 120583gmL) was found to inhibit HeLa cellproliferation (5475 inhibition) [71] Polygodial exhibitedcytotoxicity against Ehrlich ascites tumor cells and mouselymphocytic leukemia-derived L1210 cells [72]

An in vivo study performed by Raihan et al [65] showedthat the methanol (99) extract of P hydropiper aerialpart had antiproliferative activity against Ehrlich AscitesCarcinoma (EAC) cells inoculated intraperitoneally (ip)in Swiss-Webster albino male mice The extract at a doseof 50mgkgday (ip) significantly (119875 lt 0001) inhibited(8454) EAC cell growth decreased tumor weight to 785 gand improved mean survival time (680 increase of lifespan) of EAC bearing mice as compared to the positivestandard bleomycin (03mgkg ip) with values of 9855705 g and 9466 respectively


47 Anti-Inflammatory Activity Methanol (99) leaf extractof P hydropiper inhibited production of inflammatory medi-ators in vitro such as nitric oxide (NO) tumor necrosis factor(TNF)-120572 and prostaglandin (PG) E

2

in lipopolysaccharide-induced RAW2647 cells and peritoneal macrophages bysuppressing the activation of SrcSykNF-kB and IRAKAP-1CREB pathways [73]

Furuta et al [51] demonstrated the anti-inflammatoryproperty of polygonolide isolated from methanol extractof P hydropiper root by inhibiting reversed passive Arthusreaction A dose of 100mgkg polygonolide administeredorally 1 hour before induction of inflammation on the ratskin was able to inhibit 392 (119875 lt 005) of the acuteinflammation

Polygodial a major compound previously isolated fromthe barks of Drimys winteri was reported to be responsi-ble for inhibiting guinea-pig ileum and tracheal contrac-tility in vitro induced by several mediators associated withasthmatic and allergic responses including acetylcholinehistamine bradykinin KCl 911-dideoxy-9120572 11120572-methano-epoxy prostaglandin F

2120572

substance P and tachykinin NK2

receptor [74] It also showed inhibitory effect of ovalbumin-sensitized and compound 4880-stimulated contraction ofguinea-pig trachea [74] da Cunha et al [75] revealed thatpolygodial had anti-inflammatory and antiallergic propertiesin vivo via various mechanisms of actions including inhi-bition of mice paw oedema induced by prostaglandin E

2

(ID50

107 120583molkg at 180min) bradykinin (ID50

86 120583molkgat 60min) substance P (ID

50

83 120583molkg at 180min) dextran(ID50

17 120583molkg at 60min) platelet activating factor (58inhibition at 60min) carrageenan (ID

50

32 120583molkg) andovalbumin (80 inhibition at 240min) mice ear oedemawas stimulated by arachidonic acid (ID

50

1413 120583molkg) cap-saicin (ID

50

169 120583molkg) and croton oil (44 inhibition)pleurisy was induced by substance P and histamine andanaphylactic shock was stimulated by ovalbumin

48 Antinociceptive Activity Ethyl acetate extract of Phydropiper whole plant exhibited significant dose-dependentantinociceptive activity in Swiss albino mice (4286 inhi-bition at 250mgkg and 5495 at 500mgkg 119875 lt 0001)as compared to aminopyrine (7362 at 50mgkg) byacetic acid-inducedwrithingmethod suggesting its analgesicpotential [76]

Mendes et al [77] isolated polygodial from the barks ofD winteri and found that it (01 to 10mgkg administeredby intraperitoneal injection) was able to inhibit mice abdom-inal contractions induced by acetic acid (ID

50

08mgkg)zymosan (ID

50

21mgkg) and kaolin (ID50

26mgkg)Polygodial also demonstrated distinct systemic spinal andsupraspinal antinociceptive effect onmicemainly preventingthe formalin- and capsaicin-induced neurogenic pain viaseveralmechanisms including binding to the k andd subtypesof opioid receptors activation of pertussis toxin-sensitiveGiGo-protein binding to 120572

1

-adrenoceptors and serotonin-ergic system [78] Neurogenic antinociceptive and thermalantihyperalgesic effects were observed in neonatal treatmentof rats [79]

49 Oestrogenic and Antifertility Activity Garg et al [80]first reported the antifertility activity of ethanol extractof P hydropiper root on female albino rats Recently themethanol root extract administered orally to ovary-intact andovariectomized adult albino rats at a dose of 1000mgkg bodyweightday for three consecutive oestrous cycles (12 days)was found to induce endometrial proliferation and folliculargrowth that was evidenced by the regulation of endome-trial protein expression suggesting its oestrogenic propertycomparable to estradiol-17120573 [26 81] Further investigationshave demonstrated that the steroid-containing fraction ofP hydropiper methanol root extract administered subcuta-neously at a dose of 5mgkgday stimulated proliferation ofuterine epithelium of ovariectomized adult albino rats [27]The fraction also stimulated expression of various uterineproteins in ovary intact (molecular weight asymp150000 asymp90000asymp82000 asymp56000 asymp43000 and asymp38000) and ovariectomized(asymp38000) rats but reduced expression of proteins (asymp65000and asymp38000) in pregnant rats of 5-6 days after implantation[82] The latter was indicated by the suppressed expressionof estrogen-sensitive transforming growth factor-120573I in theprimary decidual zone of the implantation sites during day6 of gestation suggesting the antifertility activity [83]

410 Antiadipogenic Activity Methanol extract of P hydro-piper whole plant (1 120583gmL) and its flavonol components iso-quercitrin (50120583M) and isorhamnetin (50 120583M) were shownto activate the Wnt120573-catenin signaling in HEK 293 cellscontaining pTOPFlash reporter gene increase nuclear local-ization of 120573-catenin in 3T3-L1 adipocyte cells and inhibitadipocyte differentiation suggesting its potential applicationas antiobesity agents and for associated disorders [84]

411 Anticholinesterase Activity Cholinesterase assays usingacetylcholinesterase and butyrylcholinesterase enzymes wereconducted on P hydropiper However the methanol extractfractions (hexane dichloromethane ethyl acetate butanoland aqueous) and changweikangic acid A did not exhibitanticholinesterase activity [17 42]

412 Neuroprotective Activity Persicarin was discovered as acomponent of the P hydropipermethanol leaf extract [45] Asamatter of factMa et al [85] reported that persicarin isolatedfrom the stems and leaves ofOenanthe javanica demonstratedsignificant neuroprotective activity (408ndash745 protection at100 120583M 119875 lt 0001) in glutamate-induced neurotoxicity ofrat cortical cells by inhibition of intracellular calcium influxintracellular nitric oxide production and cellular peroxideformation aswell as by increasing the antioxidant activities ofsuperoxide dismutase glutathione reductase and glutathioneperoxidase Depending on the amount of persicarin in Phydropiper its extract could potentially possess neuroprotec-tive activity

5 Toxicology

Kuroiwa et al [86] stated that the P hydropiper ethanolleaf fraction containing 70 polygodial gave positive muta-genicity in two tests that is the Ames test using Salmonella


typhimurium TA 100 and TA 98 and the chromosomalaberrations usingChinese hamster-derivedCHLIU cells butit was negative for micronuclei in mouse bone marrow cellsIt was also previously reported that polygodial was negativelymutagenic in the Ames test using TA 100 TA 98 and TA2637 strains of S typhimurium [71] and in the mammaliancell V79HGPRT assay [87]

Acute toxicity in Swiss-Webster albino male mice wasconducted by Raihan et al [65] in which methanol (99)extract of P hydropiper aerial part (20ndash600mgkg) wasinjected intraperitoneally After 24 hours no mortality wasobserved up to 400mgkg but 100mice died at 600mgkgsuggesting the LD

50

of the extract to be 500mgkg (ip)Kuroiwa et al [86] also investigated the subchronic

toxicity of WPE in male and female F344DuCrj rats givenad libitum for 13 weeks The no observed-adverse effect wasfound with 1000 ppm ethanol leaf fraction containing 70polygodial (574 and 629mgkgday for males and femalesresp) whereby there were no obvious clinical signs andno significant changes in food consumption hematologyand serum biochemistry body and organ weights andhistopathology of organs of the tested rats

The aerial parts cause blister of the skin upon repeatedhandling that could be due to the skin irritant polygodial[49 88] Polygodial isolated from the bark of D winteri wasfound to increase extracellular glutamate concentrations viaconcurrently inhibiting glutamate uptake by rat astrocytesand slices of cortex striatum and hippocampus and increas-ing glutamate release by synaptosomes suggesting possibleneurotoxic effect of polygodial [89]

6 Conclusions

The numerous ethnobotanical uses of P hydropiper haddrawn the attention of the scientists to investigate itstraditional claims The above discussion clearly gives us aperception on the scientific evidence of different pharma-cological properties of this species which supports anumber of its traditional uses such as antibacterial antifu-ngal antihelminth antifeedant anticancer anti-inflamma-tory antinociceptive oestrogenicity and antifertility usesThe antiallergic antiadipogenic and neuroprotective prope-rties of the plant provided new knowledge on the extens-ion of its uses The plant contained several remarkable phar-macologically active compounds for example polygodialwas found to have antibacterial antifungal antifeedant anti-inflammatory antinociceptive and antiallergic propertiespolygonolide had anti-inflammatory activity Warburganalacted as antifeedant confertifolin had antibacterial andantifungal activities persicarin demonstrated neuroprote-ctive activity isoquercitrin quercetin quercetin-3-O-rham-noside 741015840-dimethylquercetin galloyl quercitrin isorha-mnetin-37-disulphate 35-dihydroxy-4-methoxybenzoicacid hydropiperoside B and vanicoside A showedantioxidant properties while isoquercitrin and isorhamnetinwere antiadipogenic Oral consumption of ethanol leaffraction containing 7 polygodial was found to be safe invivo Thus this plant serves as a promising candidate as amultipurpose herbalmedicinal agent owing to its economical

viability and being a reservoir of many significant medicinalproperties in treating diseases and ailments related tomicrobial infections inflammation pain allergy uterinedisorders fertility obesity and improvement of memory

Conflict of Interests

The authors declare that they have no conflict of interestsregarding the publication of this paper

Acknowledgments

The authors wish to thank Universiti Kebangsaan Malaysia(UKM) Zamalah and BKBP-FFAR-K009946 Grant fromUKM for financial assistance

References

[1] The International Plant Names Index 2005 httpwwwipniorgipniplantNameByVersiondoid=123908-3ampversion=11

[2] The Plant List ldquoA working list of all plant speciesrdquo 2013httpwwwtheplantlistorg

[3] Australian Plant Name Index (APNI) Integrated BotanicalInformation System (IBIS) Australian National Botanic Gar-dens Australian National Herbarium January 2014 httpwwwanbggovaucgi-binapnitaxon id=39312

[4] Flora of North America ldquoPersicaria hydropiperrdquo January 2014httpwwweflorasorgflorataxonaspxflora id=1amptaxon id=242100096

[5] Flora of Missouri ldquoPolygonum hydropiperrdquo January 2014httpwwweflorasorgflorataxonaspxflora id=610amptaxon id=200006723

[6] USDA ldquoldquoPolygonum hydropiper L marshpepper knotweedrdquoJanuary 2014 httpwwwplantsusdagovcoreprofilesymbol=POHY

[7] J A Duke M J Bogenschutz-Godwin J duCellier and P A KDuke Handbook of Medicinal Herbs CRC Press Boca RatonFla USA 2002

[8] Flora of China ldquoPolygonum hydropiperrdquo January 2014httpwwweflorasorgflorataxonaspxflora id=2amptaxon id=200006723

[9] Ethnobotanical Database of Bangladesh (EDB) 31 ldquoTaxonomicInformation Phyto-chemical Constituents amp Traditional Usesof Plantsrdquo January 2013 httpwwwethnobotanybdcomindexphpaction=Taxonomyampkey=sci

[10] I H BurkillADictionary of the Economic Products of theMalayPeninsula vol 2 Ministry of Agriculture and Co-operativesKuala Lumpur Malaysia 1966

[11] USDA ldquoGRIN taxonomy for plants Taxon Persicaria hydro-piper (L) Delarbrerdquo January 2014 httpwwwars-gringovcgi-binnpgshtmltax searchpl

[12] D T LoiTheGlossary of VietnameseMedicinal Plants and ItemsHanoi Medicine Publishing House Hanoi Vietnam 2000

[13] M Miyazawa and N Tamura ldquoInhibitory compound of tyrosi-nase activity from the sprout of Polygonum hydropiper L(Benitade)rdquo Biological and Pharmaceutical Bulletin vol 30 no3 pp 595ndash597 2007

[14] B C Das P K Sarker and M M Rahman ldquoAphidicidalactivity of some indigenous plant extracts against bean aphid


Aphis craccivoraKoch (Homoptera Aphididae)rdquo Journal of PestScience vol 81 no 3 pp 153ndash159 2008

[15] D V Banthorpe ldquoPolygonum hydropiper L (water pipper)In vitro culture and the production of the aphid-antifeedantpolygodialrdquo in Medicinal and Aromatic Plant IV Biotechnologyin Agriculture and Forestry Y P S Bajaj Ed vol 21 pp 269ndash279 Springer Berlin Germany 1993

[16] Z F Peng D Strack A Baumert et al ldquoAntioxidant flavonoidsfrom leaves of Polygonumhydropiper Lrdquo Phytochemistry vol 62no 2 pp 219ndash228 2003

[17] N H Noor Hashim F Abas K Shaari and N H LajisldquoLC-DAD-ESIMSMS characterization of antioxidant and anti-cholinesterase constituents present in the active fraction fromPersicaria hydropiperrdquo LWTmdashFood Science and Technology vol46 no 2 pp 468ndash476 2012

[18] Y Fukuyama T Sato Y Asakawa and T Takemoto ldquoA potentcytotoxic warburganal and related drimane-type sesquiter-penoids from Polygonum hydropiperrdquo Phytochemistry vol 21no 12 pp 2895ndash2898 1980

[19] Ministry of Health Labour and Welfare ldquoList of existing foodadditivesrdquo in Foods Food Ingred (Editorial) vol 166 pp 93ndash101Japan 1995 (Japanese)

[20] G A Stuart Chinese Materia Medica Vegetable KingdomSouthern Materials Centre Taipei Taiwan 1979

[21] E Blatter J F Caius andK SMhaskar IndianMedicinal PlantsPeriodical Experts Book Agency Vivek Vihar India 1998

[22] A Chevallier The Encyclopedia of Medicinal Plants DorlingKindersley London UK 1996

[23] J L Hartwell ldquoPlants used against cancer A surveyrdquo Lloydiavol 33 no 3 pp 288ndash392 1970

[24] I Tita D M George and G T Monica ldquoEthnobotanicalinventory ofmedicinal plants from the South-West of RomaniardquoFarmacia vol 57 no 2 pp 141ndash156 2009

[25] D Moerman Native American Ethnobotany Timber PressOregaon USA 1998

[26] A Hazarika and H N Sarma ldquoThe estrogenic effects of Poly-gonumhydropiper root extract induce follicular recruitment andendometrial hyperplasia in female albino ratsrdquo Contraceptionvol 74 no 5 pp 426ndash434 2006

[27] P Goswami A Hazarika and H N Sarma ldquoThin layer chro-matographic fraction of root extract of Polgonum hydropiperinduces vaginal epithelial cell maturation in adult ovariec-tomized albino ratrdquo Journal of Endocrinology Reproduction vol12 no 1 pp 39ndash46 2008

[28] R K Choudhary S Oh and J Lee ldquoAn ethnomedicinal inven-tory of knotweeds of Indian Himalayardquo Journal of MedicinalPlant Research vol 5 no 10 pp 2095ndash2103 2011

[29] N D Namsa M Mandal S Tangjang and S C MandalldquoEthnobotany of theMonpa ethnic group atArunachal PradeshIndiardquo Journal of Ethnobiology and Ethnomedicine vol 7 article31 2011

[30] R K Choudhury and R C Srivastava ldquoIPR and traditionalknowledge of Adi Memba and Khamba tribes of upper siangdistric Arunachal Pradeshrdquo inTheNational Conference on IPRPlant Varieties and Genome Conservation K Arvind Ed SPMukharjee College 2006

[31] D Mahanta and S C Tiwari ldquoNatural dye-yielding plantsand indigenous knowledge on dye preparation in ArunachalPradesh northeast Indiardquo Current Science vol 88 no 9 pp1474ndash1480 2005

[32] M Rahmatullah I J Mukti A K M Fahmidul Haque et alldquoAn ethnobotanical survey and pharmacological evaluation ofmedicinal plants used by the Garo tribal community livingin Netrakona district Bangladeshrdquo Advances in Natural andApplied Sciences vol 3 pp 402ndash418 2009

[33] S Hanif Bari and M Rahmatulla ldquoMedicinal plants of thesantal tribe residing in rajshahi district BangladeshrdquoAmerican-Eurasian Journal of Sustainable Agriculture vol 3 pp 220ndash2262009

[34] M Yusuf J Begum M N Hoque and J U ChowdhuryMedicinal Plants of Bangladesh Bangladesh Council of Scientificand Industrial Research Dhaka Bangladesh 2009

[35] A Ghani Medicinal Plants of Bangladesh Chemical Con-stituents and Uses Asiatic Society of Bangladesh DhakaBangladesh 2nd edition 1998

[36] P G Xiao and N G Wang ldquoCan ethnopharmacology con-tribute to the development of anti-fertility drugsrdquo Journal ofEthnopharmacology vol 32 no 1ndash3 pp 167ndash177 1991

[37] J A Duke and E S Ayensu Medicinal Plants of ChinaReference Publications Algonac USA 1985

[38] KAkamatsuWakanyaku Ishiyakushuppan Tokyo Japan 1970[39] K S Yusif andK F Blinova ldquoFlavonoid aglycones ofPolygonum

hydropiperrdquo Chemistry of Natural Compounds vol 20 no 5 pp625ndash626 1984

[40] X Yang B C Wang X Zhang et al ldquoSimultaneous determi-nation of nine flavonoids in Polygonum hydropiper L samplesusing nanomagnetic powder three-phase hollow fibre-basedliquid-phase microextraction combined with ultrahigh perfor-mance liquid chromatography-mass spectrometryrdquo Journal ofPharmaceutical and Biomedical Analysis vol 54 no 2 pp 311ndash316 2011

[41] M A Hawrył and M Waksmundzka-Hajnos ldquoTwo-dime-nsional thin-layer chromatography of selected Polygonum spextracts on polar-bonded stationary phasesrdquo Journal of Chro-matography A vol 1218 no 19 pp 2812ndash2819 2011

[42] R Sultana R Hossain A Adhikari et al ldquoDrimane-typesesquiterpenes fromPolygonumhydropiperrdquoPlantaMedica vol77 no 16 pp 1848ndash1851 2011

[43] P V Kiem N X Nhiem N X Cuong et al ldquoNew phenyl-propanoid esters of sucrose from Polygonum hydropiper andtheir antioxidant activityrdquo Archives of Pharmacal Research vol31 no 11 pp 1477ndash1482 2008

[44] H Haraguchi K Hashimoto and A Yagi ldquoAntioxidativesubstances in leaves of Polygonum hydropiperrdquo Journal of Agri-culture and Food Chemistry vol 40 pp 1349ndash1351 1992

[45] H Haraguchi I Ohmi S Sakai et al ldquoEffect of Polygonumhydropiper sulfated flavonoids on lens aldose reductase andrelated enzymesrdquo Journal of Natural Products vol 59 no 4 pp443ndash445 1996

[46] A Yagi T Uemura N Okamura H Haraguchi T Imoto andK Hashimoto ldquoAntioxidative sulphated flavonoids in leaves ofPolygonum hydropiperrdquo Phytochemistry vol 35 no 4 pp 885ndash887 1994

[47] Y Fukuyama T Sato I Miura and Y T Asakawa ldquoDrimane-type sesqui- and norsesquiterpenoids from Polygonum hydro-piperrdquo Phytochemistry vol 24 no 7 pp 1521ndash1524 1985

[48] V Duraipandiyan F Indwar and S Ignacimuthu ldquoAntimi-crobial activity of confertifolin from Polygonum hydropiperrdquoPharmaceutical Biology vol 48 no 2 pp 187ndash190 2010

[49] C S Barnes and J W Loder ldquoStructure of polygodial a newsesquiterpene dialdehyde from Polygonum hydropiperrdquo Austra-lian Journal of Chemistry vol 15 pp 322ndash327 1962


[50] Y Fukuyama T Sato I Miura Y Asakawa and T TakemotoldquoHydropiperoside a novel coumaryl glycoside from the root ofPolygonum hydropiperrdquo Phytochemistry vol 22 no 2 pp 549ndash552 1983

[51] T Furuta Y Fukuyama and Y Asakawa ldquoPolygonolide an iso-coumarin from Polygonum hydropiper possessing anti-infla-mmatory activityrdquo Phytochemistry vol 25 no 2 pp 517ndash5201986

[52] Y Asakawa and T Takemoto ldquoNew norsesquiterpene aldehydeand sesquiterpene hemiacetal from the seed of Polygonumhydropiperrdquo Experientia vol 35 no 11 pp 1420ndash1421 1979

[53] K Ono M Nakao M Toyota et al ldquoCatechin production incultured Polygonum hydropiper cellsrdquo Phytochemistry vol 49no 7 pp 1935ndash1939 1998

[54] M J M Hagendoorn T A M Geelen T A van Beek D C LJamar F A A Tetteroo and L H W van der Plas ldquoOccurrenceof polygodial in plant organs and tissue culture of Polygonumhydropiperrdquo Physiologia Plantarum vol 92 no 4 pp 595ndash6001994

[55] J I Sanchez-Gallego A Lopez-Revuelta J L Sardina AHernandez-Hernandez J Sanchez-Yague and M LlanilloldquoMembrane cholesterol contentsmodify the protective effects ofquercetin and rutin on integrity and cellular viability in oxidizederythrocytesrdquo Free Radical Biology and Medicine vol 48 pp1444ndash1454 2010

[56] I Kubo K-I Fujita S H Lee and T J Ha ldquoAntibacterialactivity of polygodialrdquo Phytotherapy Research vol 19 no 12 pp1013ndash1017 2005

[57] A Malheiros V C Filho C B Schmitt et al ldquoAntifungalactivity of drimane sesquiterpenes from Drimys brasiliensisusing bioassay-guided fractionationrdquo Journal of Pharmacy andPharmaceutical Sciences vol 8 no 2 pp 335ndash339 2005

[58] S H Lee J R Lee C S Lunde and I Kubo ldquoIn vitro antifungalsusceptibilities of Candida albicans and other fungal pathogensto polygodial a sesquiterpene dialdehyderdquo Planta Medica vol65 no 3 pp 204ndash208 1999

[59] I Kubo and M Taniguchi ldquoPolygodial an antifungal potentia-torrdquo Journal of Natural Products vol 51 no 1 pp 22ndash29 1988

[60] M Taniguchi Y Yano E Tada et al ldquoMode of action of polygo-dial an antifungal sesquiterpene dialdehyderdquo Agricultural andBiological Chemistry vol 52 no 6 pp 1409ndash1414 1988

[61] K Machida T Tanaka and M Taniguchi ldquoDepletion ofglutathione as a cause of the promotive effects of polygodiala sesquiterpene on the production of reactive oxygen speciesin Saccharomyces cerevisiaerdquo Journal of Bioscience and Bioengi-neering vol 88 no 5 pp 526ndash530 1999

[62] C S Lunde and I Kubo ldquoEffect of polygodial on the mitochon-drial ATPase of Saccharomyces cerevisiaerdquo Antimicrobial Agentsand Chemotherapy vol 44 no 7 pp 1943ndash1953 2000

[63] MVCastelli A F LodeyroAMalheiros S A S Zacchino andO A Roveri ldquoInhibition of the mitochondrial ATP synthesisby polygodial a naturally occurring dialdehyde unsaturatedsesquiterpenerdquoBiochemical Pharmacology vol 70 no 1 pp 82ndash89 2005

[64] K-I Fujita and I Kubo ldquoMultifunctional action of antifungalpolygodial against Saccharomyces cerevisiae involvement ofpyrrole formation on cell surface in antifungal actionrdquo Bioor-ganic and Medicinal Chemistry vol 13 no 24 pp 6742ndash67472005

[65] M O Raihan M Khalequeuzzaman A Brishti S M TareqA Hossain and S Rana ldquoAnthelmintic and Antiproliferative

activity of aerial parts of Persicaria hydropiperrdquo Der PharmasiaSinica vol 3 pp 104ndash110 2012

[66] I Kubo Y-W Lee M Pettei F Pilkiewicz and K NakanishildquoPotent army worm antifeedants from the east AfricanWarbu-rgia plantsrdquo Journal of the Chemical Society Chemical Commu-nications no 24 pp 1013ndash1014 1976

[67] Y Asakawa GW Dawson D C Griffiths et al ldquoActivity of dri-mane antifeedants and related compounds against aphids andcomparative biological effects and chemical reactivity of (-)-and (+)-polygodialrdquo Journal of Chemical Ecology vol 14 no 10pp 1845ndash1855 1988

[68] L Moreno-Osorioa M Cortes V Armstrong M Bailen andA Gonzalez-Coloma ldquoAntifeedant activity of some polygodialderivativesrdquo Zeitschrift Fur Naturforschung C A Journal ofBiosciences vol 63 pp 215ndash220 2008

[69] N Zapata F Budia E Vinuela and P Medina ldquoAntifeedantand growth inhibitory effects of extracts and drimanes ofDrimys winteri stem bark against Spodoptera littoralis (LepNoctuidae)rdquo Industrial Crops and Products vol 30 no 1 pp119ndash125 2009

[70] N Prota H J Bouwmeester and M A Jongsma ldquoCompara-tive antifeedant activities of polygodial and pyrethrins againstwhiteflies (Bemisia tabaci) and aphids (Myzus persicae)rdquo PestManagement Science vol 70 no 4 pp 682ndash688 2013

[71] I Lajter I Zupko J Molnar et al ldquoAntiproliferative activity ofPolygonaceae species from theCarpathian Basin against humancancer cell linesrdquo Phytotherapy Research vol 27 no 1 pp 77ndash852012

[72] H Anke and O Sterner ldquoComparison of the antimicrobialand cytotoxic activities of twenty unsaturated sesquiterpenedialdehydes from plants and mushroomsrdquo Planta Medica vol57 no 4 pp 344ndash346 1991

[73] Y Yang T Yu H-J Jang et al ldquoIn vitro and in vivo anti-inflammatory activities of Polygonum hydropiper methanolextractrdquo Journal of Ethnopharmacology vol 139 no 2 pp 616ndash625 2012

[74] M El Sayah V Cechinel Filho R A Yunes T R Pinheiro and JB Calixto ldquoAction of polygodial a sesquiterpene isolated fromDrymis winteri in the guinea-pig ileum and trachea ldquoin vitrordquordquoEuropean Journal of Pharmacology vol 344 no 2-3 pp 215ndash2211998

[75] F M da Cunha T S Frode G L Mendes et al ldquoAdditionalevidence for the anti-inflammatory and anti-allergic propertiesof the sesquiterpene polygodialrdquo Life Sciences vol 70 no 2 pp159ndash169 2001

[76] E Rahman S A Goni M T Rahman and M AhmedldquoAntinociceptive activity of Polygonum hydropiperrdquo Fitoterapiavol 73 no 7-8 pp 704ndash706 2002

[77] G L Mendes A R S Santos M M Campos et al ldquoAnti-hyperalgesic properties of the extract and of themain sesquiter-pene polygodial isolated from the barks of Drymis winteri(Winteraceae)rdquo Life Sciences vol 63 no 5 pp 369ndash381 1998

[78] G LMendes A R S Santos AMalheiros V Cechinel Filho RA Yunes and J B Calixto ldquoAssessment ofmechanisms involvedin antinociception caused by sesquiterpene polygodialrdquo Journalof Pharmacology and Experimental Therapeutics vol 292 no 1pp 164ndash172 2000

[79] E Andre J Ferreira A Malheiros R A Yunes and J BCalixto ldquoEvidence for the involvement of vanilloid receptorin the antinociception produced by the dialdeydes unsaturatedsesquiterpenes polygodial and drimanial in ratsrdquo Neurophar-macology vol 46 no 4 pp 590ndash597 2004


[80] S K Garg V S Mathur and R R Chaudhury ldquoScreeningof Indian plants for antifertility activityrdquo Indian Journal ofExperimental Biology vol 16 no 10 pp 1077ndash1079 1978

[81] A Hazarika and H N Sarma ldquoPolygonum hydropiper cruderoot extract mimics estrogenic properties in females evidenceof uterine protein profiles studied by sodium dodecyl sulfatepolyacrylamide gel electrophoresisrdquo Reproductive Medicine andBiology vol 5 no 2 pp 155ndash160 2006

[82] P Goswami A Hazarika and H N Sarma ldquoRoot extractof Polygonum hydropiper alters the expression of rat uterineprotein profile in presence and absence of ovary in-situ duringperiimplantation period evidence on SDA-PAGErdquo Journal ofReproduction and Contraception vol 20 no 4 pp 223ndash2362009

[83] P Goswami A Hazarika and H N Sarma ldquoChromatographicfraction ofPolygonumhydropiper rootmodulates the expressionof transforming growth factor-120573I (TGF-120573I) in rat uterus duringdays 2ndash6 of gestationrdquo Journal of Reproduction and Contracep-tion vol 22 no 3 pp 153ndash167 2011

[84] S-H Lee B Kim M J Oh et al ldquoPersicaria hydropiper (L)spach and its flavonoid components isoquercitrin and isorha-mnetin activate the Wnt-120573catenin pathway and inhibit adipo-cyte differentiation of 3T3-L1 cellsrdquo Phytotherapy Research vol25 no 11 pp 1629ndash1635 2011

[85] C J Ma K Y Lee E J Jeong et al ldquoPersicarin from waterdropwort (Oenanthe javanica) protects primary cultured ratcortical cells from glutamate-induced neurotoxicityrdquo Phytother-apy Research vol 24 no 6 pp 913ndash918 2010

[86] K Kuroiwa M Shibutani K Inoue K-Y Lee G-H Woo andM Hirose ldquoSubchronic toxicity study of water pepper extractin F344 ratsrdquo Food and Chemical Toxicology vol 44 no 8 pp1236ndash1244 2006

[87] PMorales M Andersson L Lewan andO Sterner ldquoStructure-activity relationships for unsaturated dialdehydes 6 The muta-genic activity of 11 compounds in th V79HGPRT assayrdquoMutation ResearchFundamental and Molecular Mechanisms ofMutagenesis vol 268 no 2 pp 315ndash321 1992

[88] A R Clapham T Tutin and E F Warburg Flora of the BritishIsles Cambridge University Press Cambridge UK 1952

[89] L H Martini L Cereser I Z Junior et al ldquoThe sesquiterpenespolygodial and drimanial in vitro affect glutamatergic transportin rat brainrdquoNeurochemical Research vol 31 no 3 pp 431ndash4382006

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



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OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


for a variety of traditional dishes [15ndash17]The Japanese peopleuse the young shoot as spice and garnish with raw fish suchas ldquosashimirdquo for its pungent taste [18] while the water orethanol leaf extract served as a food additive to preservepickles dressing and cooked foods [19] In Southeast Asiathe Chinese and Malays use the leaves in traditional laksadishes [16]

Most importantly P hydropiper also has a wide range oftraditional uses for medicinal purposes In Europe the planthas been used as diuretic and emmenagogue [20] and toregulate menstrual irregularities [21] In addition decoctionof thewhole plant either alone ormixedwith othermedicinalplants is also given for diarrhea dyspepsia itching skinexcessive menstrual bleeding and hemorrhoids [22] Theleaves and seeds are used in a folk medicine against cancer[23]The Romanian people in Oltenia utilized infusion of theaerial part as astringent and cicatrising as well as for gastricpulmonary problems and uterine hemorrhages [24]The useof bruised leaves and seeds as vesicants has also been reported[25]

In India theMishingwomen inAssam take the dried rootpowder of P hydropiper for termination of pregnancy andit may lead to permanent sterility if taken continuously formore than a year [26 27] Leaf rsquos juice is consumed for uterinedisorders [28] In Arunachal Pradesh the whole plant extractand ground plant paste are used as fish poisons [28 29]whereas the leaf infusion is used to relieve colic pain [30]Theplant has also been utilized as natural dyes [31]

In Bangladesh the Garo tribe uses the leaf juice formenstrual pain the leaf paste to stop bleeding and the wholeplant as pesticide for stored grains [32] Another tribe ofTripura uses the mixture of crushed P hydropiper leaf withblack pepper for headache [33] In a district of Sylhet thecrushed plant helps to arrest hemorrhage and in Rema-Kalenga the leaves are used for stomach pain [34] The leafjuice has been given for treating many health problems likeheadache pain toothache liver enlargement gastric ulcerdysentery loss of appetite and dysmenorrhea while the rootsare used as stimulant and their juice is applied towounds skindiseases and painful carbuncles [35]

In Vietnam the stems and leaves are taken for snake-biteand as diuretic and anthelmintic [12] In China the plant isconsumed to prevent ovulation and cease pregnancy [36]while the root is used as stimulant diuretic carminativetonic and anthelmintic [37]

This plant has been found to be toxic to pigs and sheep[38]

3 Phytochemical Constituents

P hydropiper has been reported to contain mainly flavonoidssesquiterpenes sesquiterpenoids and phenylpropanoids(Table 1)

Various extracts and fractions ofP hydropiperwhole plantand herbs were found to contain flavonoids such as (+)-catechin (minus)-epicatechin hyperin isoquercitrin (Figure 1)isorhamnetin (Figure 1) kaempferol quercetin (Figure 1)quercitrin rhamnazin and rutin [39ndash41] drimane-typedsesquiterpenes such as 3-120573-angeloyloxy-7-epifutronolide

7-ketoisodrimenin changweikangic acid A dendocarbin L(+)-fuegin futronolide polygonumate and (+)-winterin[42] phenylpropanoid esters including hydropiperosides Aand B (Figure 1) and vanicosides A (Figure 1) B and E [43]as well as phenolic acids such as caffeic acid chlorogenic acidand 120588-coumaric acid [41]

Methanol (80ndash100) extract of the leaves had mainlyflavonoids including apigenin-7-O-glucoside galloyl kaemp-ferol-3-O-glucoside galloyl quercetin-3-O-glucoside gall-oyl quercetin-3-O-rhamnoside galloyl quercitrin (Figure 1)isoquercitrin isoquercitrin-3-glucoside isorhamnetin isor-hamnetin-37-disulphate (Figure 1) kaempferol rutinosidekaempferol-3-O-glucoside percicarinpersicarin quercitrinquercetin (Figure 1) quercetin-3-O-glucoside quercetin-3-O-120573-D-glucuronide quercetin-3-O-rhamnoside (Figure 1)quercetin-3-sulphate rhamnazin rhamnazin-3-sulphaterhamnetin scutillarein tamarixetin-3-O-120573-glucoside-7-sul-phate 31015840-methylquercetin 6-hydroxyluteolin 6-hydroxy-luteolin-7-O-120573-D-glucopyranoside 6-hydroxyapigenin and741015840-dimethylquercetin (Figure 1) [16 17 44ndash46] pheny-lpropanoids such as hydropiperosides and vanicosides A Band D and 35-dihydroxy-4-methoxybenzoic acid (Figure 1)[17] Additionally the leaf diethyl ether extract was foundto have sesquiterpenes and sesquiterpenoids such as con-fertifolin (Figure 1) drimenol (+)-fuegin isodrimeninolisopolygodial isopolygonal polygodial (Figure 1) polygodialacetal polygonal polygonic acid polygonone valdiviolidewarburganal (Figure 1) and 11-ethoxycinnamolide [18 47]whereas the essential oil had acetic acid confertifolin diethy-leneglycol monoacetate ethyl benzene ethyl propionate andn-propyl acetate [48]

The methanol extract of stems and leaves was reportedto contain hydropiperosides A and B and vanicosides AB and E [43] while the petroleum extract of top parthad polygodial [49] and the methanol extract of roots hadanthraquinone ellagic acid 331015840-di-O-methyl ether gallicacid hydropiperosides and polygonolide (Figure 1) [50 51]Several sesquiterpenes and sesquiterpenoids such as con-fertifolin drimenol isodrimeninol isopolygodial polygo-dial polygonal and warburganal have been isolated fromdiethyl ether extract of the seeds [18 52] (+)-catechin (+)-epicatechin and (+)-epicatechin-3-O-gallate were producedby the callus and suspension-cultured cells of P hydropiper[53] whereas polygodial was detected in the shoot cultures[54]

4 Pharmacological Properties

Several reports on pharmacological properties of P hydro-piper are available to support the ethnomedicinal uses ofthe plant including antioxidant antibacterial antifungalantihelminth antifeedant cytotoxicity anti-inflammatoryantinociceptive oestrogenicity anti-fertility anti-adipogeni-city anticholinesterase and neuroprotection Toxicologicaleffects of P hydropiper are also described

41 Antioxidant Activity Flavonoids are powerful antioxi-dants that can protect the human body from free radicals[55] Isoquercitrin and 7 41015840-dimethylquercetin isolated from




Flavonoids



























Table 1 Continued


Phenylpropanoids





















Others








O

OH

OH

OIsorhamnetin

OO

OO SO O

SO

O

O

OQuercetin

O

O

O

O

O

O

O

OO

O

O

OO

Hydropiperoside B

O

O HConfertifolin

CHO

CHO

H

Polygodial

O

OO

O

Isoquercitrin

O

OO

O C

OH

O

O

O

Galloyl quercitrin

O

O

O OOH

O

O

OPolygonolide

O

O

O

O

O

O

O

O

O

O

O

O

O

Vanicoside A

H

H

H

OO

Warburganal

OH

OH

OH

OHOH

OHOH

OHOH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OHOH OH

OH

OHOH

OH

OH

OH

OH

OHOH

HO

HO

HOHO

HO

HO

HO HOHO

HO

HO

HO

HO

HO

HO

HO

OCH3

H3CO

CH3

CH3

CH3

CH3

CH2OH

H3C

H3C

CH3

CH3

H3CO

H3C

H3C

CH3

CH3

CH3

CH3

OCH3

H3CO

OCH3

OCH3

OCH3

H3CO

H3CO





Ominus

minus

O




50




50


50


50


50


50



50

680120583gmL)












2




2120572



2

(ID50



50



50


50


50




50

08mgkg)zymosan (ID

50



1






5 Toxicology





50




6 Conclusions





Acknowledgments


References




































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















Flavonoids



























Table 1 Continued


Phenylpropanoids





















Others








O

OH

OH

OIsorhamnetin

OO

OO SO O

SO

O

O

OQuercetin

O

O

O

O

O

O

O

OO

O

O

OO

Hydropiperoside B

O

O HConfertifolin

CHO

CHO

H

Polygodial

O

OO

O

Isoquercitrin

O

OO

O C

OH

O

O

O

Galloyl quercitrin

O

O

O OOH

O

O

OPolygonolide

O

O

O

O

O

O

O

O

O

O

O

O

O

Vanicoside A

H

H

H

OO

Warburganal

OH

OH

OH

OHOH

OHOH

OHOH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OHOH OH

OH

OHOH

OH

OH

OH

OH

OHOH

HO

HO

HOHO

HO

HO

HO HOHO

HO

HO

HO

HO

HO

HO

HO

OCH3

H3CO

CH3

CH3

CH3

CH3

CH2OH

H3C

H3C

CH3

CH3

H3CO

H3C

H3C

CH3

CH3

CH3

CH3

OCH3

H3CO

OCH3

OCH3

OCH3

H3CO

H3CO





Ominus

minus

O




50




50


50


50


50


50



50

680120583gmL)












2




2120572



2

(ID50



50



50


50


50




50

08mgkg)zymosan (ID

50



1






5 Toxicology





50




6 Conclusions





Acknowledgments


References




































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table 1 Continued


Phenylpropanoids





















Others








O

OH

OH

OIsorhamnetin

OO

OO SO O

SO

O

O

OQuercetin

O

O

O

O

O

O

O

OO

O

O

OO

Hydropiperoside B

O

O HConfertifolin

CHO

CHO

H

Polygodial

O

OO

O

Isoquercitrin

O

OO

O C

OH

O

O

O

Galloyl quercitrin

O

O

O OOH

O

O

OPolygonolide

O

O

O

O

O

O

O

O

O

O

O

O

O

Vanicoside A

H

H

H

OO

Warburganal

OH

OH

OH

OHOH

OHOH

OHOH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OHOH OH

OH

OHOH

OH

OH

OH

OH

OHOH

HO

HO

HOHO

HO

HO

HO HOHO

HO

HO

HO

HO

HO

HO

HO

OCH3

H3CO

CH3

CH3

CH3

CH3

CH2OH

H3C

H3C

CH3

CH3

H3CO

H3C

H3C

CH3

CH3

CH3

CH3

OCH3

H3CO

OCH3

OCH3

OCH3

H3CO

H3CO





Ominus

minus

O




50




50


50


50


50


50



50

680120583gmL)












2




2120572



2

(ID50



50



50


50


50




50

08mgkg)zymosan (ID

50



1






5 Toxicology





50




6 Conclusions





Acknowledgments


References




































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















O

OH

OH

OIsorhamnetin

OO

OO SO O

SO

O

O

OQuercetin

O

O

O

O

O

O

O

OO

O

O

OO

Hydropiperoside B

O

O HConfertifolin

CHO

CHO

H

Polygodial

O

OO

O

Isoquercitrin

O

OO

O C

OH

O

O

O

Galloyl quercitrin

O

O

O OOH

O

O

OPolygonolide

O

O

O

O

O

O

O

O

O

O

O

O

O

Vanicoside A

H

H

H

OO

Warburganal

OH

OH

OH

OHOH

OHOH

OHOH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OHOH OH

OH

OHOH

OH

OH

OH

OH

OHOH

HO

HO

HOHO

HO

HO

HO HOHO

HO

HO

HO

HO

HO

HO

HO

OCH3

H3CO

CH3

CH3

CH3

CH3

CH2OH

H3C

H3C

CH3

CH3

H3CO

H3C

H3C

CH3

CH3

CH3

CH3

OCH3

H3CO

OCH3

OCH3

OCH3

H3CO

H3CO





Ominus

minus

O




50




50


50


50


50


50



50

680120583gmL)












2




2120572



2

(ID50



50



50


50


50




50

08mgkg)zymosan (ID

50



1






5 Toxicology





50




6 Conclusions





Acknowledgments


References




































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















50




50


50


50


50


50



50

680120583gmL)












2




2120572



2

(ID50



50



50


50


50




50

08mgkg)zymosan (ID

50



1






5 Toxicology





50




6 Conclusions





Acknowledgments


References




































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















2




2120572



2

(ID50



50



50


50


50




50

08mgkg)zymosan (ID

50



1






5 Toxicology





50




6 Conclusions





Acknowledgments


References




































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















50




6 Conclusions





Acknowledgments


References




































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Review Article Ethnobotanical, Phytochemical, Pharmacological, and Toxicological Aspects of...

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Transcript of Review Article Ethnobotanical, Phytochemical, Pharmacological, and Toxicological Aspects of...