International Journal of Pharmacy and Pharmaceutical Sciences Academic Sciences ISSN- 0975-1491 Vol 6 Issue 2, 2014

Review Article THE GENUS POLYGONUM (POLYGONACEAE): AN ETHNOPHARMACOLOGICAL AND PHYTOCHEMICAL PERSPECTIVES –REVIEW

GANAPATHI NARASIMHULU1, KESIREDDY KATHYVEVELU REDDY2, JAMALUDIN MOHAMED1* 1Programme of Biomedical Science, School of Diagnostic and Applied Health Science, Faculty of Health Science, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia, 2Division of Molecular Biology, Department of Zoology, S.V. University, Tirupati 517502, A.P., India. Email: [email protected] Received: 20 Jan 2014, Revised and Accepted: 02 Mar 2014 ABSTRACT The genus Polygonum (Polygonaceae), comprising about 300 species, is distributed worldwide, mostly in north temperate climates, is interesting from both biological and phytochemical perspectives. In this review, a contemporary summary of biological and pharmacological investigate on Polygonum species will be presented and critically evaluated. Significant findings in the treatment various diseases such as snake-bites, inflammatory, anticancer, antibacterial, antivirus, antiseptic, antifungal, diabetic, hypertension, hyperlipemia, jaundice, hemorrhage, cough, fever, ulcers, skin affections, anemia, diarrhea and various urologic disorders, have been presented in ethnobotanical reports and recent studies were performed on ethanol extracts for certain Polygonum species. Polygonum, the most important constituent isolated is known to possess anticancer activity. Very few additional data are available on the biological activities and cytotoxicity of pure compounds from Polygonum. Twenty-nine distinguished species of Polygonum have been reported in scientific literature as ethnobotanically used or phytochemically investigated. However, information about a chemical outline is available only for few species. The following review gives a critical assessment of the literature to date and aims to show that the pharmaceutical potential of this genus has been underestimated and deserves closer attention. Keywords: Polygonum, Traditional medicine, Pharmacology, Phytochemistry.

INTRODUCTION et al., [16]reported that evaluate the antifungal properties of aerial parts of P. acuminatum. The plant kingdom continues to be a foremost source of novel natural products with potential for use as drugs or pharmaceutical Polygonum amplexicaule mediators. According to The World Health Organization, more than 80% of the world population in developing countries depends Emodin-8-O-β-D-glucoside of P. amplexicaule significantly primarily on plants based medicines for basic healthcare needs[1]. stimulated cell proliferation at 0.1-100 μg/mL and the proportion of Polygonum is a member of Polygonaceae family that contains, cells in S-phase amplified from 16.33 to 27.29% in osteoblastic according to respective taxonomic treatments; ca. 300 species is MC3T3-E1 cells. Moreover, ethanol extracts of P. amplexicaule distributed worldwide in temperate climates[2]. They vary widely improved alkaline phosphatase (ALP) expression in MC3T3-E1 cells from prostrate herbaceous annual plants under 5 cm high, others at the concentration from 0.1 to 100 μg/mL and inhibited PGE (2) erect herbaceous perennial plants growing to 3 - 4 m, and yet others production induced by TNF-α in osteoblasts at the concentrations perennial woody vines growing up to 20-30 m high in trees. Several ranging from 10 to 100 μg/mL in MC3T3-E1 osteoblasts [20]. are aquatic, growing as floating plants in ponds. Polygonum aviculare The leaves are 1- 30 cm long, and vary in shape between species The supplementation of P. aviculare ethanol extract to high-fat diet- from narrow lanceolate to oval, broad triangular, heart-shaped, or induced obese mice significantly decreased body weight gain, adipose arrowhead forms. The stems are often red-speckled or reddish. tissue weight, adipocyte size, and lipogenic gene expression as well as Flowers are small, white, pink or greenish, appearance in summer in dark cluster from the leaf joints or stem apices. A number of serum triglyceride, leptin, and malondialdehyde (MDA) levels [21]. Polygonum species are used as food and for traditional folk Polygonum bistorta medicines such as cardiovascular protection [3], antiinflammation[4], neuroprotection [5] and mitigation of Ethanolic extract of P. bistorta showed strong antiinflammatory biochemical processes involved in age-related neurodegenerative effect[22]. Nikawa et al.,[23] reported that the aqueous extract disorders such as Alzheimer’s [6]and Parkinson’s disease[7]. strongly inhibits the mutagenicity of Trp-P-1. The hexane and chloroform fractions and their sub-fractions were evaluated for their Chemical constituents recognized in the Polygonum species are cytotoxic activity against P338 (Murine lymphocytic leukaemia), flavonoid [8], triterpenoids [9], anthraquinones [10], coumarins [11], HepG2 (Hepatocellular carcinoma), J82 (Bladder transitional phenylpropanoids [12, 13], lignans [14], sesquiterpenoids [15, 16], carcinoma), HL60 (Human leukaemia), MCF7 (Human breast cancer) stilbenoids [17], and tannins [2]. Amongst them, flavonoids are the most and LL2 (Lewis lung carcinoma) cancer cell lines in culture [24]. common components found in Polygonum and have previously been used as chemotaxonomic markers of the genus, playing an important Polygonum capitatum role in the systematics of Polygonaceae species[18]. Ethanolic extracts of P. capitatum possessed antibacterial, , Present study is an attempt to compile an up-to-date and comprehensive antiinflammatory, hypothermia, diuretic and antioxidative activities [25]. review of the genus Polygonum that covers its traditional medicinal uses, chemistry and pharmacology. Many plants of this genus are Polygonum chinense pharmacologically known but chemically unknown and vice-versa, The chloroform and ethanol extract of whole plant of P. chinense therefore, the scope of future research in this aspect. demonstrated a strong activity against Bacillus subtilis, Stapphylococcus Ethnobotanical studies aureus, Pseudomonas aeruginosa, Aspergillus niger [26]. Polygonum acuminatum Polygonum Cillinerve Aerial parts of P. acuminatum, are used to heal infected wounds and The administration of P. Cillinerve with gavage was able to overcome for other disorders related to fungal infections[19].Recently Derita the cyclophosphamide-induced immunosuppression and

Mohamed et al. Int J Pharm Pharm Sci, Vol 6, Issue 2, 21-45 significantly to raise the total oxidant capacity (TOC), catalase (CAT), (TPA) as a promoter [13]. Methanolic extract of P. lapathifolium superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) stems have potential anthelmintic and anti-emetic properties [46]. level. It also raised the liver, spleen, thymus indices and decreased the malondialdehyde (MDA) level in mice [27]. Polygonum limbatum Polygonum cuspidatum Methanol extract and compounds of P. limbatum have showed cytotoxicity and antimicrobial activity[47]. Extract of P. cuspidatum has antiinflammatory activities such as inhibition of NF-kB have been reported [4, 28]. Polydatin of P. Polygonum minus cuspidatum has favorable potency to develop a hypolipemic and Various researchers reported the different biological and hepatoprotective agent in clinic [29]. Ethanol and ethyl acetate pharmacological activities of Polygonum minus in both in vitro and in extracts of P. cuspidatum root exhibit an antiproliferative effect on vivo experimental models. It has been found to exhibit antiulcer human lung cancer cells[30]. Piceid of P. cuspidatum represents a [48], antimicrobial [49], antioxidant, anticytotoxicity and safe and new candidate for a skin-lightening agent[31]. 2-methoxy- antigenotoxicity activities [50]. 6-acetyl-7-methyljuglone may act as a potent anti-oxidant, which significantly interferes with the Mitogen-activated protein kinases Polygonum multiflorum apoptotic cascades, probably rescuing cells by inhibiting the death This herb possesses many effects, such as lipid lowering, pathways [32]. Han et al., [33]reported that ethyl acetate extract of P. antioxidation, toxin detoxification, anti-tumor, and lubricating cuspidatum can be a potent candidate for rheumatoid arthritis treatment. intestine, to treat cardiovascular disorders, neurological disorders, Extract of P. cuspidatum shown that possesses wound-healing activity and other diseases commonly associated with aging [51, 52]. [34]. Resveratrol and emodin have shown anticancer potential in various Modern chromatographic separation studies have demonstrated cancer cells, including hepatocarcinoma cells [35, 36]. that many bioactive compounds in P. multiflorum, e.g. stilbene Polygonum ferrugineum glycosides, are responsible for its medicinal activities [53-55]. 2,3,5,4’-Tetrahydroxystilbene-2-O-beta-d-glucosidel, a major active Lopez et al., [37]reported that P. ferrugineum extracts as used to heal stilbene glycoside in P. multiflorum, has been reported to possess infected wounds and as antiseptic, antibiotic antifungal agent in antioxidative, antiinflammatory, endothelial protective, and traditional medicine. oncogenic enzyme inhibitory activities [56]. Hexane extract of P. Polygonum flaccidum multiflorum neuroprotective effect against glutamate-induced neurotoxicity via inhibition of apoptosis[57]. Mazid et al., [38]reported that alpha-santalone, of P. flaccidum could be a potent candidate for analgesic and the diuretic. Polygonum odoratum Polygonum glabrum The n-Butanol fraction from the methanol extract of this herb exhibited dramatic hypoglycemic effects in STZ-induced diabetic P. glabrum extract is clinically effective as antiinflammatory drug mice [58].Chia et al.,[59]reported that the water extract of rhizome and works by the mechanism of action similar to that of nonsteroidal of P. odoratum decreased the blood level in starch-loaded antiinflammatory drugs (NSAIDs), also has been researched for mice. anthelmintic activity [39].Which showed activity against Hymenolepis nana var. fraternal. Kiron et al.,[40] reported that Polygonum orientale analgesic activity of aqueous extract of P. glabrum has performed by Water extract of P. orientale comprising flavonoids as its principles formalin-induced paw licking in rats. was of potential use in the treatment of cardiovascular and Polygonum hypoleucum cerebrovascular diseases and an injection prepared from the flavonoid-enriched water extract had demonstrated protective P. hypoleucum Ohwi is a Chinese herbs that has been used for the effects on myocardial ischaemia [60]. Leaves and flowers of P. treatment of arthritis, rheumartitis, cough, influenzaand nephritis orientale showed a protective effect on H9c2 myocardial cells [41]. The previous studies found that P. hypoleucum is a growth oxidative injury [61]. A flavonoid-enriched extract of P. orientale was modulator for tumor cells and human mesangial cells [42]. reported to show cardioprotective effect[62]. Polygonum hyrcanicum Polygonum paleaceum Aerial parts of the Polygonum hyrcanicum are used for the treatment Recently, a few pharmacological studies showed that extract of P. paleaceum has antiinflammatory effect on inflammatory rates and of liver problems, anemia, hemorrhoids and kidney stones[43]. antitumor activity to K562, HL-60 (Human promyelocytic leukemia Methanolic extract from aerial parts of P. hyrcanicum showed high activity against Trypanosoma brucei rhodesiense (IC50 = 3.7 cells) in vitro and S180, Hep A in vivo, which are related to oxygen microg/mL)[44]. free radical scavenging and antilipid peroxidation activity of P. paleaceum[63]. Polygonum lanatum Polygonum perfoliatum Oral administration of either hexane, and ethyl acetate extracts at a Recently, contemporary studies have shown that P. perfoliatum has a dose of 300 mg/kg body weight showed statistically significant (p < variety of pharmacological functions including antiinflammatory 0.001) inhibition of rat paw edema by 41.09% and 30.15%, respectively, which was comparable to that of standard drug [64], antibacterium [65] and antitumor effects. Pharmacological phenylbutazone (42.15%). Compared to the inhibition of acetic acid- studies indicated that the flavonoids in P. perfoliatum have antiviral, induced writhing by aminopyrine (69.94%, p < 0.001), treatment anti-oxidative andantitumor activities [66]. with either hexane, or ethyl acetate extracts or methanol extracts Polygonum punctatum elicited significant inhibition of acetic acid-induced writhing reflex by 44.80% (p < 0.001), 33.87% (p < 0.01) and 62.29% (p < 0.001), Previous pharmacological reports with the ethanol/water extract of respectively. In addition, mild to potent diuretic activity was the entire P. punctatum disclosed antifungal, antihistaminic, observed after oral administration of these extracts in swiss albino antiinflammatory, antipyretic and hypotensive activities [67]. mice[45]. Polygonum sachalinensis Polygonum lapathifolium Previous work showed that leaves extracts of P. sachalinensis can be Phenylpropanoid esters of , vanicoside B and lapathoside A, used as a plant fungicide against powdery mildew that flavonones of P. lapathifolium exhibited significant antitumor-promoting effects and anthraquinones of flower extracts are good antioxidant on mouse two-stage skin carcinogenesis induced by 7,12- compounds and that phenylpropanoid glycosides from the rhizomes dimethylbenz [a] anthracene and tetradecanoyl phorbol acetate exhibit β-glucosidase inhibitory activity[68].

22 Mohamed et al. Int J Pharm Pharm Sci, Vol 6, Issue 2, 21-45

Polygonum spectabile Polygonum viscosum Geraldo et al., [69]reports on the investigation of the antimicrobial Ethanolic extract of young shoots of P. viscosum was found to and antiviral activity of different extracts and compounds isolated possess antibacterial activity [74]. from the aerial parts of P. spectabile. Polygonum viviparum Polygonum stagninum It is used as a folk remedy to treat inflammation related diseases. On the antiinflammatory response of P. viviparum against The n-hexane, ethyl acetate and methanol extracts of the aerial parts lipopolysaccharide (LPS)-induced inflammation in RAW264.7 of P. stagninum were assessed for analgesic and antiinflammatory macrophages [75]. properties in experimental mice and/or rat models[70]. Chemical constituents Polygonum tinctorium The reported data showed that flavonoids, terpenoids coumarins, Antifungal, cancer chemopreventive and antibacterial activities [71, fatty acid, cinnamic acid derivatives, steroids and alkaloids are the 72].Yu et al., [73]reported that the potent anti-HIV-1 and HSV-1 main and common phytochemicals of the genus Polygonum. The activity of an aqueous extract from the fermented leaves of P. reported phytochemicals from different plants of the genus are given tinctorium while seeds and leaves of P. tinctorium have an as following. antioxidant and anticancer properties.

Polygonum acuminatum Polygodia (1), isopolygodial (2), drimenol (3), confertifolin (4)[16].

(1) (2) (3) (4)

Polygonum amplexicaule (11)[77]. 5, 6-dihydropyranobenzopyrone (12), amplexicine (13), catechin (14), rutin (15), quercetin-3-O-β-D-galactopyranoside (16), Friedelin (1), 훽 −sitosterol (2), simiarenone (3), angelicin (4), chlorogenic acid (17), galloyl glucose (18), caffeic acid (19), gallic psoralen (5), palmitic acid (6), (-)-epicatechin (7), quercetin (8)[76], acid (20), scopletin (21) [77]. Emodin-8-O-β-D-glucoside (9) [20], flavan-3-ol (10), khellactone

(1) (2) (3)

(4) (5) (6)

(7) (8) (9)

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(10) (11) (12)

(13) (14) (15)

(16) (17) (18)

(19) (20) (21)

Polygonum aviculare Polygonum bistorta Avicularin (1), kaempferol (2), quercetin (3), myricetin (4), 3-O-methyl-gallic acid (1), quercetin-3-O-β-D-glucopyranoside (2) [80], cafferic acid (5), chlorogenic acid (6), coumaric acid (7), oxalic 5-glutinen-3-one (3), friedelanol (4) [9], 24(E)-ethylidenecycloartanone acid (8), D-catechin (9), gallic acid (10) [78], naphthoquinone (5), 24(E)-ethylidenecycloartan-3a-ol (6), cycloartane-3, 24-dione (7), (11), 6-methoxyplumbagin (12), β-sitosterol (13), oleanolic acid 24-methylenecycloartanone (8), c-sitosterol (9), β-sitosterol (10), β - (14), 5,6,7,4’-tetramethoxyflavanone (15) [79]. sitosterone (11), friedelin (12), 3-β -friedelinol (13) [24, 81].

(1) (2) (3)

(4) (5) (6)

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(7) (8) (9)

(10) (11) (12)

(13) (14) (15)

(1) (2) (3)

(4) (5) R=O, (6) R=α − OH,

(7). R1 =O (9) (8). R1= CH2

25 Mohamed et al. Int J Pharm Pharm Sci, Vol 6, Issue 2, 21-45

(10) (11) (12)

(13)

(1) (2) (3)

(4) (5) (6)

(7) (8) (9)

(10) (11) (12)

26 Mohamed et al. Int J Pharm Pharm Sci, Vol 6, Issue 2, 21-45

(13) (14) (15)

(16) (17) (18)

(19) (20) (21)

(22) (23) (24)

(25) (26) (27)

(28)

Polygonum capitatum nimbecetin (8), quercetin (9), quercitroside (10), tetracosylferulate (11), quercetin-3-O-휷-D-glucoside (12), β-deucosterol (13), β- Gallic acid (1), quercitrin (2), vanillic acid (3), protocatechuic acid sitosterol (14), [83]. Schizandriside (15), (-)-isolariciresinol-2a-O- β (4), flavones (5), chromone glycoside (7-O-(6′-Galloyl)-β-D- -D-xylopyranoside (16), (-) -5 ‘-methoxy isolariciresinol-2a-O-훃-D- glucopyranosyl-5-hydroxychromone) (6) [82],progallin A (7), xylopyranoside (17), nudiposide (18), [84] 5,7-dihydroxy-4H-

27 Mohamed et al. Int J Pharm Pharm Sci, Vol 6, Issue 2, 21-45 chromen-4-one (19), ellagic acid (20), myricetrin (21), hirsutine Polygonum chinense (22), rutin (23), quercetin-3-O-(2”-O-galloyl)-훃-D-glucopyranoside (24) quercitrin (25), kaempferol-3-O-휶-L-rhamnopyranoside (26), Squalene (1), 1,2-benzenedicarboxylic acid (2), 1,2- quercetin-3-O-(2”-O-galloyl)-훂-L-rhamnopyranoside (27), benzenedicarboxylic acid, mono [2-ethylhexyl] ester (3), 4-hexene- kaempferol (28) [85]. 1-ol, 5-methyl-2-(methylethanyl)-acetate-®-(4) [86].

(1) (2) (3)

(4) Polygonum Cillinerve Emodin-8-β-D-(2″-O-coumarate) glucoside (1), emodin-8-β- D-(6´-O-acetyl) glucoside (2), physicon-8-β-D-(6´-O-acetyl) glucoside (3) [10].

(1) (2). R= OH, (3). R = OCH3

Polygonum cuspidatum trihydroxybenzoate) (8), (+)- catechin-3-O-gallate (9) [89], resveratroloside (10), 3,5,5-trihydroxystilbene-3-O- (6”-galloy)- Piceid (5,4’-dihydroxystilbene-3-O-β-D-glucopyranoside) (1) glucoside (11), emodin-1-O-glucoside (12), torachrysone-8- [87], 2-methoxy-6-acetyl-7-methyljuglone (2) [88], 2- Oglucoside (13), emodin-8-O-glucoside (14), emodin-8-O-(6’- methoxystypandrone (3), emodin (4), resveratrol (5), polydatin malonyl)-glucosideb (15), torachrysone-8-O-(6’-acetyl)- (6), emodin-8-O-β-D-glucopyranoside (7), (E)-3, 5, 12- glucoside (16), physcion-8-O-glucoside (17), physcion-8-O-(6’- trihydroxystilbene-3-O- β-D-glucopyranoside-2’- (3”, 4”, 5”- acetyl)-glucoside (18)[90].

(1) (2) (3)

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(4) (5) (6)

(7) (8) (9)

(10) (11) (12)

(13) (14) (15)

(16) (17) (18)

Polygonum ferrugineum hydroxymethyl-b-hydroxy-dihydrochalcone (2), pashanone (3), flavokawin B (4), cardamonin or alpinetin chalcone (5), 5,7-dihydroxy-6-methoxy-3- (9-hydroxy-phenylmethyl)- pinostrobin (6) 5,8-dimethoxy-7-hydroxychroman-4-one (7)[8], chroman-4-one (1), 2’4’6’- trihydroxy-30-methoxy-a- chalcone (8)[37].

(1) (2) (3)

(4) (5) (6)

(7) (8)

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Polygonum hypoleucum Emodin (1), physcion (62A) (2), emodin 1-O-β-D-glucoside (49A) (3), physcion 1-O-β-D-glucoside (50A)(4), emodin-8-O-β-D-glucopyranoside (5), (+)-catechin (6), (-)-epicatechin (7) [91, 92].

(1). R1=R2=H, (2). R1=H, R2=CH3 (3). 훽 – (5,) (6) D-glucoside, R2=H, (4). 훽 -D-glucoside, R2=CH3

(7)

Polygonum hyrcanicum gallocatechin (9)[98], myricetin 3-O-β-D-galactopyranoside (10) myricetin 3-O-α-L-rhamnopyranoside (myricitrin) (11)[99], Quercetin (1), myricetin (2)[93] [17], N-trans-caffeoyltyramine quercetin 3-O-β-D-galactopyranoside (12)[100], quercetin,3-O-α-L- (3)[94], quercetin 3-O-α-L-(3”,5”-diacetyl-arabinofuranoside) arabinofuranoside (avicularin) (13)[101], tyrosol (14), p-coumaric (4)[95], quercetin 3-O-α-L-(3”-acetyl-arabinofuranoside) (5), acid (15), ferulic acid (16), N-cis-feruloyltyramine (16), N-trans-p- myricetin 3-O-α-L-arabinofuranoside (6)[96], myricetin 3-O-α-L- coumaroyltyramine (17), N-trans-3,4- (3”,5”-diacetyl-arabinofuranoside) (7)[97], (+) catechin (8), (-) dimethoxycinnamoyldopamine (18)[44].

(1). R1=H, R2=H, (3) (4). R1=-COOH3, R2=COCH3, (2). R1=H, R2=OH, (5). R1=-COCH3, R2=H, (10). R1= β-D-galactopyranoside, R2=OH, (13). R1=H R2=H, (11). R1= β α-L-rhamnopyranoside, R2=OH, (12).R1= β-D-galactopyranoside, R2=H.

(6). R1=H R2=H, (8). R=H (14) (7). R1=-COOH3, R2=COCH3, (9). R=OH

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(15) (16) (17)

(18) (19)

Polygonum lapathifolium Vanicoside B (1), lapathoside A (2)[13], 5-hydroxy-7-methoxy flavanone (pinostrobin) (3) [102].

(1) (2) (3)

Polygonum limbatum Cardamomin (1), (±)-polygohomoisoflavanone (2), (S)-(−)-pinostrobin (3), 2′,4′-dihydroxy-3′,6′-dimethoxychalcone (4), (2S)-(-)-5-hydroxy-6,7- dimethoxyflavanone (5), (2S)-(-)-5,7-dimethoxyflavanone (6) [47].

(1) (2) (3)

(4) (5) (6)

Polygonum minus selinene (31), valencene (32), δ-cadinine (33), alloaromadendrene (34), α-curcumene (35), (-)-α-panasinsene (36), cis –lanceol (37), Decanal (1), dodecanal (2), decanol (3), 1-dodecanol, (4), undecanal farnesol (38), humulene (39), nerolidol (40), dodecanoic acid (41), (5), tetradecanal (6), 1-undecanol (7), nonanal (8), 1-nonanol (9), β- β-caryophyllene oxide (42), trans-α-(Z)-Bergamotol (43), Caryophyllene (10)[103], rutin (11), catechin (12), quercetin (13), tetradecanal (44), alloaromadendrene oxide-(1) (45), trans- isorhamnetin (14), hexanal (15)[104], 1-hexanol (16), α-Pinene longipinocarveol (46), neoisolongifolene,8-bromo- (47) iso- (17), kaempferol (18), undecane (19), nonanal (20), 1-nonanol (21), caryophyllene (48),drimenol (49), drimenin (50), phytol (51) [105], isobornyl acetate (22), n-decanoic acid (23), α-cubebene (24), 6,7-methylenedioxy- 5,3‟,4‟,5‟ tetramethoxyflavone (52), 7-4‟,5‟- xanthorrhizol (25), (E)-caryophyllene (26), trans-α-bergamotene dimethylenedioxy-3,5,3‟-trimethoxyflavone (53) [106]. (27), α-bisabolol (28), farnesene (29), β-himachalene (30), α-

31 Mohamed et al. Int J Pharm Pharm Sci, Vol 6, Issue 2, 21-45

(1) (2) (3)

(4) (5) (6)

(7) (8) (9)

(10) (11) (12)

(13) (14) (15)

(16) (17) (18)

(19) (20) (21)

(22) (23) (24)

(25) (26) (27)

(28) (29) (30)

32 Mohamed et al. Int J Pharm Pharm Sci, Vol 6, Issue 2, 21-45

(31) (32) (33)

(34) (35) (36)

(37) (38) (39)

(40) (41) (42)

(43) (44) (45)

(46) (47) (48)

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(49) (50) (51)

(52) (53)

Polygonum multifloruma apigenin (10), daucosterol (11), β -sitosterol (12), stearic acid (13)[108],5-methyl-2-(1-methylethyl) phenyl- β-D- Tetrahydroxystilbene-glucoside (2,3,5,4’-tetrahydroxystilbene- glucopyranoside(14) [109], hyperoside (15), rutin (16), vitexin 2-O- β-D-glucoside) (1)[107], Chrysophanol (2), physcion (3), (17), β -amyrin (18) [110], gallic acid (19), hypaphorine (20), emodin (4), aloeemodin (5), rhein (6), physcion-8-O- β-D- catechin (21), proanthocyanidin B1(22), proanthocyanidin B2 glucoside (7), emodin-8-O- β-D-glucoside (8), noreugenin (9), (23), epicatechin (24) [111].

(1) (2) (3)

(4) (5) (6)

(7) (8) (9)

(10) (11) (12)

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(13) (14) (15)

(16) (17) (18)

(19) (20) (21)

(22) (23) (24)

Polygonum odoratum β-caryophyllene (16), allo-aromadendren (17),훼-caryophyllene (18), eremophillene (19), 7-epi-alpha-selinene (20), ledol (21), (Z)-3-hexenal (1), (Z)-3-hexenol (2) decanal (3), undecanal (4), nerolidol (22), globulol (23), caryophyllene oxide (24), cubenol (25), dodecanal (5), aldehydes (6), 3-sulfanyl-hexanal (7), 3-sulfanyl- eupatoriochromene (26), drimenol (27), hexahydro farnesyl acetone hexan-1-ol (8) [112], (9), undecane (10), 1-nonanol, (11) (28), isophytol (29), n-hexadecanoic acid (30)[113] saponin (31), decanol (12), n-decanoic acid (13), 1-nonene (14), β-elemene (15), flavonoid (32) [114].

(1) (2) (3)

(4) (5) (6)

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(7) (8) (9)

(10) (11) (12)

(13) (14) (15)

(16) (17) (18)

(19) (20) (21)

(22) (23) (24)

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(25) (26) (27)

(28) (29) (30)

(31) (32) Polygonum orientale hydroxyphenylethanol-p-coumaric (15) catechin (16), isoorientin (17), orientin (18), quercetin-3-O-(2”-O- 훼-rhamnopyranosyl) -훽- alphitonin (1), methyl 3, 4-dihydroxybenzoate (2), apocynin (3), glucarono-pyranoside (19), taxifoliol (20), luteolin (21)[116], kaempferol-3-O-훽-D-glucoside (4), 1,3,5-trihydroxybenzene (5), ombuine-3-O-훽-D-galactopyranoside (22), ombuine-3-O-rutinoside 3,3’-dimethoxyellagic-acid-4-O- 훽 -D-glucoside (6), kaempferol-3-O- (23)[117], tryptophan (24), quercetin-3-O-methyl ether (25), 훼-L-rhamnoside (7), quercetin-3-O-훼-L-rhamnoside (8), kaempferol kaempferol-3-O-(2”-O- 훼-L-rhamnopyranosyl) -훽-D- (9) [115], 3,5,7-trihydrochromone (10), 5,7,4’- glucuronopyranoside (26), quercetin-3-O-훽-D-glucuronide (27) trihydroxydihydroflavonol (11), dihydroquercetin (12), quercetin [118], gallic acid (28), alphitonin (29), taxifolin (30), kaempferol-3- (13), p-hydroxyphenylethanol ferulate (14), p- O-훽-D-glucoside(31)[119].

(1) (2) (3)

(4) (5) (6)

(7) (8) (9)

(10) (11) (12)

37 Mohamed et al. Int J Pharm Pharm Sci, Vol 6, Issue 2, 21-45

(13) (14) (15)

(16) (17) (18)

(19) (20) (21)

(22) (23) (24)

(25) (26) (27)

(28) (29) (30)

(31)

38 Mohamed et al. Int J Pharm Pharm Sci, Vol 6, Issue 2, 21-45

Polygonum paleaceum procyanidin C1 (7), chlorogenic acid (8), methyl 5-O- caffeoylquinate (9), 3-O-caffeoyl quinic acid (10), rutin (11), Paleaceolactoside (1), 6-O-galloyl-glucose (2), (+)-catechin (3), quercetin-3-O-β-d-glucuronide (12), caffeic acid (13), gallic acid (−)-epicatechin (4), procyanidin B1 (5), procyanidin B2 (6), (14) [2].

(1) (2) (3). R= 훽 −OH, (4). R=훼 − OH

(5). R=훼 − OH, (7) (8). R1= R3 =H, R2=caffeoy, (6). R=훽 − OH (9). R1=CH3, R2=caffeoy (10). R1= R3 =H, R2=caffeoy,

(11) (12) (13)

(14) Polygonum perfoliatum (7), 1’2’6’-triacetyl-3,6-diferuloylsucrose (8), 2’6’-diacetyl-3,6- diferuloylsucrose (9),1,3,6-tri-p-coumaroyl-6’- feruloyl sucroses 4-dihydro-4-(4’-hydroxyphenyl)-5,7-dihydroxycoumarin (1), (10), vanicoside A (11), vanicoside B (12) [120], quercetin-3-O- 3,4-dihydro-5-hydroxy-7-methoxy-4-(4’-methoxyphenyl) β-D-glucuronide (13) [65], 5-hydroxymethyl-2-furaldehyde (14), coumarin (2), 3,4-dihydro-5-hydroxy-4-(4’-hydroxyphenyl)-7- methyl caffeoate (15), protocatechuic aldehyde (16), quercetin methoxycoumarin (3), 3,4-dihydro-5,7-dihydroxy-4-(4’- (17), pinocernbrin (18), catechin (19), taxifolin (20), taxifolin-3- methoxyphenyl) coumarin (4)[11], 6’-acetyl-3,6- O- 훽-D-xylopyranoside (21), 13-epitorulosal (22), coumarin-7-O- diferuloylsucrose (helonioside B) (5), 2’4’6’-triacetyl-3,6- 훽-D-glucose glycosidic (23) [121], 8-oxo-pinoresinol (24), 3’,5- diferuloylsucrose (6), 1’2’4’6’-tetraacetyl-3,6-diferuloylsucrose dihydroxy-3,4’,5’,7-tetramethoxy-flavone (25), rutin (26) [122].

(1) (2) (3)

39 Mohamed et al. Int J Pharm Pharm Sci, Vol 6, Issue 2, 21-45

(4) R1 R2 R3 R4 R5 R6

(5) H H H H H COCH3

(6) H H COCH3 H COCH3 COCH3

(7) COCH3 H COCH3 H COCH3 COCH3

(8) COCH3 H COCH3 H H COCH3

(9) H H COCH3 H H COCH3

(10) (11) R= -COCH3 (12) R=H

(13) (14) (15)

(16) (17) (18)

(19) (20) (21)

(22) (23) (24)

40 Mohamed et al. Int J Pharm Pharm Sci, Vol 6, Issue 2, 21-45

(25) (26)

Polygonum punctatum Polygodial (1)[123].

(1) Polygonum sachalinensis feruloyltyramine (4), lapathoside C (5), hydropiperoside (6), vanicoside B (7) [124], phenylacetonitrile (8), (E)-β-ocimene (9), Quercetin-3-O-β-D-galactopyranoside (1), quercetin-3-O- (10), (E)-4,8-dimethyl-1,3,7-nonatriene (11), (E,E)-α- arabinopyranoside (2), lapathoside D (3), N-trans- farnesene (10) [125].

(1) (2) (3)

(4) (5) (6)

41 Mohamed et al. Int J Pharm Pharm Sci, Vol 6, Issue 2, 21-45

(7) (8) (9)

(10) (11) (12) Polygonum viscosum 3’,5-dihydroxy-3,4’,5 ‘,7-tet- ramethoxyfavone (1), quercetin 3-O-(6-feruloyl)-β-D-galactopyranoside (2), 4-isobutyl-6-methyl-5-oxo-3a,4,5,7a- tetrahydro- 1H-inden-13-oic acid (3) [15].

(3) R1 R2 R3

(1) Me Me Me

(2) H 6-feruloyl- 훽 -D-galactopyranosyl H

(4) H 6-caffeoyl-훽 −D-galactopyranosyl H

CONCLUSION for their preliminary in vitroactivities; so, the advance clinical trial of them deserves to be further investigated. Herein, we described the Although, an extensive amount of research work has been done on possible applications in clinical research but further investigations some plants of this genus to date, the isolated compounds from this on phytochemical discovery and subsequent screenings are needed genus are belong to terpenoids, flavonoids, coumarins, fatty acid, for opening new opportunities to develop pharmaceuticals based on cinnamic acid derivatives, steroids and alkaloids but some of species Polygonum constituents. are still chemically and/or pharmacologically unknown such as P. flaccidum, P. glabrumP. lanatum, P.spectabile, P. stagninumP. REFERENCES tinctorium, and P. viviparum. Consequently, a broad field of future research remains possible in which the isolation of new active 1. Peter H, Canter HT, Edzard E. Bringing medicinal plants into principles from these species would be of great scientific merit. cultivation: opportunities and challenges for biotechnology. However, the mechanism of their action is still unknown. Trends in Bioteh2005; 23(4): 180-185. 2. Wang KJ, Zhang YJ, Yang CR. Antioxidant phenolic compounds Hence, a detailed study is required to understand the structure– from rhizomes of Polygonum paleaceum. J Ethnopharmacol activity relationship of these constituents. As literature showed, 2005; 96(3): 483-7. many plant extracts having cytotoxic activity, antitumor, 3. Yim TK, Wu WK, Pak WF, Mak DH, Liang SM, Ko KM. Myocardial antimicrobial, antibacterial, analgesic, anti-inflammatory, protection against ischaemia-reperfusion injury by a hypothermia, diuretic, and anti-oxidative activities, hence, the Polygonum multiflorum extract supplemented 'Dang-Gui particular constituent responsible for the activity may be isolated for decoction for enriching blood', a compound formulation, ex further process. In addition, some plant extracts were only screened vivo. Phytother Res 2000; 14(3): 195-9.

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