Letters
in the meantime. Herbal treatments have demonstrated some
Anti-HIV Activities of the Compounds
Isolated from Polygonum cuspidatum
and Polygonum multiflorum
Hong-Wei Lin 1*, Ming-Xue Sun 1*, Yun-Hua Wang 2, Liu-Meng
Yang 2, Ying-Ruo Yang 2, Ning Huang 2, Li-Jiang Xuan 3, Ya-Ming
Xu 3, Dong-Lu Bai 3, Yong-Tang Zheng 2, Kai Xiao 1
1
Lab of Toxicology & Pharmacology, Faculty of Naval Medicine, The
Second Military Medical University, Shanghai, P. R. China
2
Key Laboratory of Animal Models and Human Disease Mechanisms
of Chinese Academy of Sciences & Yunnan Province, Kunming Insti-
tute of Zoology, Chinese Academy of Sciences, Kunming, P. R. China
3
Shanghai Institute of Materia Medica, Shanghai Institutes for Biolog-
ical Sciences, Chinese Academy of Sciences, Shanghai, P. R. China
Abstract
! possess various bioactivities [12]. Anti-virus activities such as
The 70 % EtOH extract of Polygonum cuspidatum showed inhibi-
tory action against HIV-1-induced syncytium formation at non-
cytotoxic concentrations in vitro with a 50% effective concentra-
tion (EC50) of 13.94 ± 3.41 µg/mL. Through bioactivity-guided
fractionation, 20 phenolic compounds, including eight stilbe-
noids, were isolated from the roots of Polygonum cuspidatum,
and their anti-HIV‑1 activities were evaluated. Results showed
that compounds 1, 13, 14, and 16 demonstrated fairly strong
antiviral activity against HIV-1-induced cytopathic effects in
C8166 lymphocytes at non-cytotoxic concentrations, with EC50
values of 4.37 ± 1.96 µg/mL, 19.97 ± 5.09, 14.4 ± 1.34 µg/mL, and
11.29 ± 6.26 µg/mL and therapeutic index (TI) values of 8.12,
> 10.02, > 13.89, and > 17.71, respectively. Other compounds
showed either weak or no effects. Compound 6 also showed weak
inhibition (153.42 ± 19.25 µg/mL); however, it possesses very
good water solubility and showed almost no cytotoxicity
(> 2000 µg/mL), therefore achieving a fairly good TI (13.04). The
activities of the two compounds (3 and 18) from Polygonum mul-
tiflorum were also assayed. The relationship between molecular
structures and their bioactivities was also discussed.
Key words
Polygonum cuspidatum · Polygonum multiflorum · Polygona-
ceae · chemical components · anti‑HIV‑1 activity
Supporting information available online at
http://www.thieme-connect.de/ejournals/toc/plantamedica
Acquired immunodeficiency syndrome (AIDS), caused by human
immunodeficiency virus (HIV), has become the leading cause of
death in Africa and the fourth worldwide since the first reported
case in 1981 [1, 2]. The number of people with HIV-1 is also in-
creasing at an alarming rate in China and other Asian countries.
Although the anti-HIV-1 drugs now available have improved the
quality of life of HIV/AIDS patients, the appearance of drug-resis-
tant viruses and severe side effects have driven the search for
new anti-HIV-1 agents and targets. Many people, especially those
in the developing countries, have turned to traditional medicine
* These authors contributed equally to this work.
benefits in AIDS therapy, and many compounds exhibiting anti-
HIV activity have been screened, including alkaloids, sulfated pol-
ysaccharides, polyphenolics, flavonoids, coumarins, lignans, ribo-
some-inactivating proteins, saponins, quinines, peptides, and
others [3, 4]. Natural products provide a large reservoir for
screening of anti-HIV-1 agents with novel structures and anti-vi-
ral mechanisms because of their structural diversity.
The dried root of Polygonum cuspidatum Sieb. et Zucc. (Polygona-
ceae) is one of the most commonly used so-called heat-clearing
and detoxicating remedies in traditional Chinese medicine, and
it has been widely used for the treatment of hepatitis, suppura-
tive dermatitis, gonorrhea, favus, athleteʼs foot, and hyperlipemia
in China and Japan. Anthraquinones [5], stilbenes [6–8], flavo-
noids, and other phenols [5] have been isolated from this plant
previously. Recently we reported the new stilbene glycoside sul-
fates [9], lignan sulfates [10], and dimeric stilbene glycosides [11]
isolated from the water-soluble fraction of this plant. The stil-
benes, especially resveratrol and piceid, have been reported to
anti-HBV and anti-HSV have been reported for this plant [13,
14]. Furthermore, Jiang et al. reported the anti-HIV activity of
the water extract of P. cuspidatum [15], which aroused our inter-
est to investigate the anti-HIV components in this plant.
Through bioactivity-guided fractionation, some phenolic com-
pounds were separated and purified from the 70 % EtOH extract
of P. cuspidatum roots by combined column chromatography
techniques. The structures of these compounds were established
by means of comparison with the literature data and spectro-
scopic methods as (E)-resveratrol (1), piceid (2) [16], sodium
trans-resveratrol-3-O-β-D-glucopyranoside-6′′-sulfate (4), sodi-
um trans-resveratrol-3-O-β-D-glucopyranoside-4′′-sulfate (5),
sodium trans-resveratrol-3-O-β-D-glucopyranoside-2′′-sulfate
(6), sodium trans-resveratrol-3-O-β-D-glucopyranoside-4′-sul-
fate (7), sodium trans-resveratrol-3-O-β-D-glucopyranoside-5-
sulfate (8), sodium trans-resveratrol-3-O-β-D-glucopyranoside-
4′-sulfate (9) [9], (−)-lyoniresinol-2a-sulfate (10), sodium (+)-iso-
laricireinol-2a-sulfate (11) [10], (−)-epicatechin-5-O-β-D-gluco-
pyranoside (12) [17], 5,7-dimethoxyphthalide (13) [18], (+)-cate-
chin (14) [19], (+)-catechin-7-O-β-D-glucopyranoside (15) [20],
emodin-8-O-β-D-glucopyranoside (16) [16], sodium 3,4-dihy-
droxy-5-methoxybenzoic acid methyl ester-4-sulfate (17) [10],
1-(3-O-β-D-glucopyranosyl-4,5-dihydroxyphenyl)-ethanone (19)
[21], chlorogenic acid (20) [22], isotachioside (21), and tachioside
(22) [21]. Moreover, the antiviral activities of the eluates and the
compounds were evaluated through assays for cytotoxicity and
anti-HIV‑1 activity according to the previously described proto-
col [23] and are summarized in l " Table 1 and Table 2.
2,3,4′,5-Tetrahydroxy-trans-stilbene-2,3-di-O-β-D-glucopyrano-
side (3) and indole-3-(L-α-amino-α-hydroxypropionic acid)
methyl ester (18), previously isolated from the roots of Polygo-
num multiflorum [24], were also assayed. Their chemical struc-
tures are shown in l " Fig. 1.
Among the stilbenoids, resveratrol (1) showed the strongest in-
hibitory activity against HIV replication (EC50: 4.37 ± 1.96 µg/mL)
with a TI of 8.14. However, when the 3-hydroxy group was glyco-
sylated, the inhibition dropped significantly (the EC50s of com-
pounds 2 and 4−8 are all > 200 µg/mL), revealing that the free
phenolic groups were vital for the observed activity in the stil-
bene skeleton. Compound 6 achieved a better TI (13.04), though
it showed moderate suppression of HIV replication (EC50:
153.42 ± 19.25 µg/mL). This result may be attributed to its good
Lin H-W et al. Anti-HIV Activities of … Planta Med
 Letters

Extracts and eluates CC50a (µg/mL) EC50b (µg/mL) TIc Table 1 Anti-HIV‑1 activities of
Crude extract 158.41 ± 3.44 13.94 ± 3.41 11.36 extracts and eluates from P. cuspi-
Water-soluble 107.54 ± 13.25 7.84 ± 0.75 13.72 datum.
Water-insoluble 126.54 ± 9.46 12.74 ± 0.60 9.93
Fr. A > 200 > 200
Fr. B > 200 81.55 ± 10.79 > 2.45
Fr. C > 200 106.41 ± 7.30 > 1.88
Fr. D > 200 87.85 ± 3.12 > 2.28
Fr. E 184.64 ± 5.16 14.66 ± 2.88 12.59
Fr. F 163.67 ± 4.36 7.83 ± 4.51 20.90
Fr. G 125.94 ± 1.67 4.88 ± 0.34 25.81
Fr. H 92.67 ± 3.82 12.71 ± 2.77 7.29
Fr. Ai 58.88 ± 11.10 6.72 ± 1.24 8.76
Fr. Bi 106.4 ± 9.6 58.38 ± 9.45 1.82
Fr. Ci > 200 16.56 ± 7.43 > 12.08
Fr. Di 141.31 ± 19.55 5.55 ± 0.99 25.46
AZT 1146.08 ± 103.21 0.00296 ± 0.00 065 387, 189.2
a
Concentration that inhibits uninfected C8166 cell growth by 50%. Results are expressed as the mean ± SD of three independent experi-
ments; b Concentration that inhibits viral replication by 50%. Results are expressed as the mean ± SD of three independent experiments;
c
Therapeutic index = CC50/EC50

Compound Source CC50 (µg/mL)a EC50 (µg/mL)b TIc Table 2 Summary of cytotoxicity
1 P. cuspidatum 35.57 ± 1.73 4.37 ± 1.96 8.14 and anti-HIV‑1 activities of com-
2 P. cuspidatum > 200 > 200 pounds from Polygonum species.
3 P. multiflorum > 200 176.26 ± 24.26 > 1.13
4 P. cuspidatum 745.85 ± 10.84 > 200 < 3.73
5 P. cuspidatum 812.88 ± 18.90 > 200 < 4.06
6 P. cuspidatum > 2000 153.42 ± 19.25 > 13.04
7 P. cuspidatum > 2000 > 200
8 P. cuspidatum 526.52 ± 2.61 89.66 ± 1.65 5.87
9 P. cuspidatum 98.82 ± 6.23 84.77 ± 4.09 1.17
10 P. cuspidatum > 200 71.06 ± 13.10 > 2.81
11 P. cuspidatum 143.21 ± 1.62 74.9 ± 2.6 1.91
12 P. cuspidatum 181.97 ± 2.05 58.88 ± 10.14 3.09
13 P. cuspidatum > 200 19.97 ± 5.09 > 10.02
14 P. cuspidatum > 200 14.4 ± 1.3 > 13.89
15 P. cuspidatum 165.96 ± 21.79 47.86 ± 6.26 3.47
16 P. multiflorum > 200 11.29 ± 6.26 > 17.71
17 P. cuspidatum > 200 109.65 ± 24.03 > 1.82
18 P. multiflorum > 200 83.32 ± 7.85 > 2.40
19 P. cuspidatum > 200 46.25 ± 23.54 > 4.32
20 P. cuspidatum > 200 85.11 ± 3.20 > 2.40
21 P. cuspidatum > 200 55.08 ± 9.41 > 3.63
22 P. cuspidatum 1460 ± 151 > 200 < 7.30
AZT 1288.24 ± 123.76 0.0049 ± 0.0011 262, 906.12
a
Concentration that inhibits uninfected C8166 cell growth by 50%. Results are expressed as the mean ± SD of three independent experi-
ments; b Concentration that inhibits viral replication by 50%. Results are expressed as the mean ± SD of three independent experiments;
c
Therapeutic index = CC50/EC50

water solubility and significantly reduced cytotoxicity
(> 2000 µg/mL). Compared with compounds 4–8, it seems that
the position of the sulfate group has no influence on the activity
of compound 6. While the stereochemistry of the double bond
bears some relationship with the activity, the cis isomer (com-
pound 9, EC50: 84.77 ± 4.09 µg/mL) is more active than its trans
counterpart (5, EC50: > 200 µg/mL). However, the cis isomer is al-
so more cytotoxic. It was reported that resveratrol (1) possesses
potent synergistic inhibitory activity against HIV-1 infection in
combination with nucleoside analogs [25]. Compared with com-
pounds 14 and 15, it seems that the free hydroxy group at C-7 is
important for resveratrolʼs activity. The activities of compounds
21 and 22 indicated that the arrangement of the same groups also
affects their inhibitory activity. Of all the isolated compounds,
stilbenoids, anthraquinones, catechins, and some other phenolic
compounds exhibited anti-HIV-1 activities, which partly explains
the “heat-clearing and detoxicating” function of this herb used in
China and the antiviral activities previously described. Further
investigation into the mechanisms and synergic effects of these
compounds needs to be carried out in future studies.
Materials and Methods
!
The cell line used in this study (C8166) was maintained in RPMI-
1640 medium supplemented with 10% heat-inactivated new-
born calf serum (Gibco). The cells used in all experiments were

Lin H-W et al. Anti-HIV Activities of … Planta Med


in log-phase growth. The laboratory-derived virus HIV-1IIIB was
obtained from MRC, AIDS Reagent Project, United Kingdom. The
50 % HIV-1 tissue culture infectious dose (TCID50) in C8166 cells
was determined and calculated by the Reed and Muench method.
Virus stocks were stored in small aliquots at − 70 °C. The titer of
virus stock was 9 × 105 TCID50 per milliliter. 3′-Azido-3′-deoxy-
thymidine (AZT) was purchased from Sigma (purity > 99%); 2-
mercaptoethanol was obtained from Bio-Rad; and RPMI-1640
and heat-inactivated newborn calf serum were from Gibco. The
purity of all the compounds was assessed by HPLC, NMR, and
ESI‑MS or FAB‑MS and ranged from 95% (11) to 99 % (1). Unless
stated otherwise, all other chemicals used in the assay experi-
ment were purchased from Sigma.
The roots of Polygonum cuspidatum Sieb. et Zucc. were purchased
from HuaYu Drug Corporation, Ltd. and were identified by the
author. A voucher specimen (No. PC001) is deposited at the Her-
barium of the Pharmacy School of the Second Military Medical
University, Shanghai, P. R. China.
The air-dried roots of Polygonum cuspidatum Sieb. et Zucc. (6 kg)
were extracted with 70 % aqueous EtOH under reflux for 2 h
(3 × 60 L). EtOH was evaporated under vacuum and the hydro-
phobic substances were precipitated and filtered. The filtrate
(water-soluble portion) was concentrated and chromatographed
on Diaion HP20 macropore polymeric adsorbent (200 ~ 600 µm;
Letters
Fig. 1 Chemical structures of compounds 1–22
from P. cuspidatum and P. multiflorum.
Mitshubishi Chemical) eluted with aqueous MeOH (10–90 %) to
give eight fractions (Fr. A – Fr. H). Fr. B was repeatedly chromato-
graphed on Toyopearl HW40F (32–63 µm; Tosoh) eluted with
aqueous MeOH gradiently to afford compounds 4 (30 mg), 5
(12 mg), and 6 (25 mg). Fr. D was repeatedly chromatographed
on MCI CHP20P (Mitshubishi Chemical; 25% MeOH) and Toyo-
pearl HW-40F (10% MeOH) to give 7 (8 mg), 8 (14 mg), and 9
(10 mg). Fr. E was subjected to MCI gel CHP20P chromatography
(30% MeOH) and purified on ODS (Cosmosil 75C18-OPN 75 µm;
Nacalai Tesque Inc.; 20% MeOH) to give 10 (11 mg), 11 (15 mg),
and 17 (27 mg). Fr. F was chromatographed on Toyopearl HW40F
(10% MeOH) and purified with ODS (20 % MeOH) to give 19
(13 mg), 21 (27 mg), 22 (16 mg), and the crystal 2 (20 g). Fr. G
was repeatedly chromatographed on Toyopearl HW40F (40 %
MeOH) and ODS (20 % MeOH) to yield 15 (100 mg), 12 (17 mg),
and 20 (12 mg). Fr. H was chromatographed on an MCI CHP20P
column (90 % MeOH) to afford crystal 16 (1.0 g).
Part of the precipitate (water-insoluble portion, 30 g of 180 g)
was subjected to silica gel column chromatography using CHCl3
with increasing MeOH stepwise to give fractions Ai–Di. Fraction
Ai (5.1 g) was further separated by silica gel (CHCl3−MeOH
20 : 1–10 : 1) to produce subfractions 1 and 2. Subfraction 1
(860 mg) was chromatographed by gel filtration on Sephadex
LH-20 (70 µm; Amersham Bioscience; CHCl2−MeOH 1 : 1) to give
Lin H-W et al. Anti-HIV Activities of … Planta Med
 Letters

crystal 1 (85 mg), while subfraction 2 (260 mg) was further sepa- deficiency syndrome. Virol Sin (Zhongguo Bingduxue) 1998; 13: 306–
311
rated on ODS C18 (50 µm; YMC Co.; 50% MeOH) to afford 14
16 Ngoc TM, Minh PTH, Hung TM, Thuong PT, Lee IS, Min BS, Bae K. Lipoxy-
(12 mg). Fr. Ci (4.2 g) was chromatographed on MCI gel CHP20P genase inhibitory constituents from rhubarb. Arch Pharm Res 2008;
(40% MeOH) to afford the crystal 13 (40 mg). Fraction Di (6.0 g) 31: 598–605
was separated on silica gel (MeOH−CHCl3 1 : 1–5 : 1) to produce 2 17 Cui CB, Tezuka Y, Kikuch T, Nakano H, Tamaoki T, Park JH. Constituents
(120 mg), 15 (22 mg), and 16 (2.0 g). All compounds underwent of a fern, Davallia mariesii Moore. Isolation and identification of a novel
norcarotane sequiterpene glycoside, a chromone glucuronide, and two
spectrum analysis to identify their chemical structures.
epicatechin glycosides. Chem Pharm Bull (Tokyo) 1992; 40: 2035–2040
The cellular toxicity of eluates and compounds on C8166 cells 18 Sun MX, Li X, Liu WY, Xiao K. 5,7-Dimethoxyisobenzofuran-1 (3H)-one.
was assessed by the MTT method as described previously [26]. Acta Crystallogr E 2009; 65: o2146
The syncytium reduction assay was carried out according to the 19 Thompson RS, Jacques D, Haslam E, Tanner RJN. Plant proanthocyani-
reference protocol [27]. Detailed protocols are available in the dins. Part I. Introduction; the isolation, structure, and distribution in
nature of plant procyanidins. J Chem Soc [Perkin I] 1972: 1387–1399
Supporting Information.
20 Takani M, Nakano M, Takahashi K. Studies on constituents of medicinal
plants. XIX. Constituents of Schizandra nigra MAX. (3). Chem Pharm
Supporting information Bull (Tokyo) 1977; 25: 3388–3390
Detailed protocols for the cytotoxicity assay and for the syncyti- 21 Xiao K, Xuan LJ, Xu YM, Bai DL. Studies on the chemical constituents of
Polygonum cuspidatum. Chin Pharm J 2003; 38: 12–14
um reduction assay are available as Supporting Information.
22 Sano K, Sanada S, Ida Y, Shoji J. Studies on the constituents of the bark of
Kalopanax pictus Nakai. Chem Pharm Bull (Tokyo) 1991; 39: 865–870
Acknowledgements 23 Zhang GH, Wang Q, Chen JJ, Zhang XM, Tam SC, Zheng YT. The anti-HIV‑1
! effect of scutellarin. Biochem Biophys Res Commun 2005; 334: 812–
The authors are grateful for financial support from the National 816
24 Xiao K, Xuan LJ, Xu YM, Bai DL. Novel stilbene glycosides from Polygo-
Natural Science Foundation of China (20872179 and 30472141),
num multiflorum. Acta Bot Sin 2002; 44: 1491–1494
the Science and Technology Commission of Shanghai Municipal- 25 Heredia A, Davis C, Redfield R. Synergistic inhibition of HIV‑1 in acti-
ity (STCSM) (08DZ1971504), the Scientific and Technological vated and resting peripheral blood mononuclear cells, monocyte-de-
Projects of China (2009ZX09501–029, 2008ZX10005–005), the rived macrophages, and selected drug-resistant isolates with nucleo-
973 Program (2009CB522306), and the CAS (KSCX1-YW-R-24, side analogues combined with a natural product, resveratrol. J Acquir
Immune Defic Syndr 2000; 25: 246–255
KSCX2-YW-R-185). We would also like to acknowledge the MRC
26 Zheng YT, Zhang WF, Ben KL, Wang JH. In vitro immunotoxicity and cy-
AIDS Research Project and the NIH AIDS Research and Reference totoxicity of trichosanthin against human normal immunocytes and
Reagent Program for providing cell lines and viruses. leukemia-lymphoma cells. Immunopharmacol Immunotoxicol 1995;
17: 69–79
References 27 Zheng YT, Ben KL, Jin SW. Anti-HIV‑1 activity of trichobitacin, a novel
ribosome-inactivating protein. Acta Pharmacol Sin 2000; 21: 179–182
1 Fauci AS. Twenty-five years of HIV/AIDS. Science 2006; 313: 409
2 UNAIDS. The 2008 Report on the global AIDS epidemic. Available at
http://www.unaids.org/en/KnowledgeCentre/HIVData/GlobalReport/
received October 22, 2009
2008/2008_Global_report.asp. Accessed September 1, 2009
3 Singh IP, Bharate SB, Bhutani KK. Anti-HIV natural products. Curr Sci revised December 12, 2009
2005; 89: 269–290 accepted December 16, 2009
4 Asres K, Seyoum A, Veeresham C, Bucar F, Gibbons S. Naturally derived
anti-HIV agents. Phytother Res 2005; 19: 557–581 Bibliography
5 Kimura Y, Kozawa M, Baba K, Hata K. New constitutents of roots of DOI http://dx.doi.org/10.1055/s-0029-1240796
Polygonum cuspidatum. Planta Med 1983; 48: 164–168 Published online
6 Kubo M, Kimura Y, Shin H, Haneda T, Tani T, Namba K. Studies on the Planta Med
antifungal substances of crude drugs (II). On the roots of Polygonum © Georg Thieme Verlag KG Stuttgart · New York ·
cuspidatum Sieb. et Zucc. (Polygonaceae). Shoyakugaku Zasshi 1981; ISSN 0032‑0943
35: 58–61
7 Jayatilake GS, Jayasuriya H, Lee ES, Koonchanok NM, Geahlen RL, Ashen- Correspondence
del CL, McLaughlin JL, Chang CJ. Kinase inhibitors from Polygonum cus- Prof. Dr. Yongtang Zheng
pidatum. J Nat Prod 1993; 56: 1805–1810 Key Laboratory of Animal Models and Human Diseases Mechanisms and
8 Hegde VR, Pu H, Patel M, Black T, Soriano A, Zhao W, Gullo VP, Chan TM. Laboratory of Molecular Immunopharmacology
Two new bacterial DNA primase inhibitors from the plant Polygonum Kunming Institute of Zoology
cuspidatum. Bioorg Med Chem Lett 2004; 14: 2275–2277 Chinese Academy of Sciences
9 Xiao K, Xuan L, Xu Y, Bai D. Stilbene glycoside sulfates from Polygonum Kunming
cuspidatum. J Nat Prod 2000; 63: 1373–1376 Yunnan 650223
Peopleʼs Republic of China
10 Xiao K, Xuan L, Xu Y, Bai D, Zhong D. Constituents from Polygonum cus-
Phone: + 86 87 15 19 56 84
pidatum. Chem Pharm Bull (Tokyo) 2002; 50: 605–608 Fax: + 86 87 15 19 56 84
11 Xiao K, Xuan L, Xu Y, Zhong D, Wang Z, Zhang N. Dimeric stilbene glyco- zhengyt@mail.kiz.ac.cn
sides from Polygonum cuspidatum. Eur J Org Chem 2002: 564–568
12 Xiao K, Zhang HJ, Xuan LJ, Zhang J, Xu YM, Bai DL. Stilbenoids: chemistry Correspondence
and bioactivities. In: Atta-ur-Rahman, editor. Studies in natural prod- Associate Prof. Dr. Kai Xiao
ucts chemistry. Amsterdam: Elsevier B.V.; 2008: 453–646 Lab of Toxicology & Pharmacology
13 Chang JS, Liu HW, Wang KC, Chen MC, Chiang LC, Hua YC, Lin CC. Ethanol Faculty of Naval Medicine
extract of Polygonum cuspidatum inhibits hepatitis B virus in a stable The Second Military Medical University
HBV-producing cell line. Antiviral Res 2005; 66: 29–34 800 Xinangyin Road
Shanghai 200433
14 Wang ZJ, Wang XY, Chen ZM. Research about antiviral effect of ethyl
Peopleʼs Rapublic of China
acetate component of Rhizoma Polygoni cuspidati on herpes virus Phone: + 86 21 81 87 11 29
hominis. Zhongguo Xiandai Yongyong Yaoxue Zazhi 1999; 16: 27–31 Fax: + 86 21 81 87 11 28
15 Jiang Y, Wan H, Bao Z, Zhu G. Evaluation of antiviral effect of Polygonum kaixiaocn@gmail.com
cuspidatum water extract with a model of murine acquired immuno-

Lin H-W et al. Anti-HIV Activities of … Planta Med