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Fo-ti

Scientific Name(s): Polygonum multiflorum Thunb.
Common Name(s): Chinese cornbind, Climbing knotweed, Flowery knotweed, Fo-ti, Heshouwu, Radix Polygoni multiflori, Tuber fleeceflower

Medically reviewed by Drugs.com. Last updated on Dec 24, 2018.

Clinical Overview

Use

Evidence exists of hepatic injury in humans. P. multiflorum and its extracts should be considered hepatotoxic; however, the plant is widely used in traditional Chinese medicine and Ayurvedic medicine for its rejuvenating and toning properties, to increase liver and kidney function, for treatment of cognitive disorders and dyslipidemia, and to cleanse the blood. Clinical trials are lacking to support claims for therapeutic purposes, but topical applications for the treatment of alopecia and a role in neurodegenerative diseases are being investigated.

Dosing

P. multiflorum is used at daily doses of 9 to 15 g of raw herb, but clinical studies are lacking. A standard dose in the Chinese Pharmacopoeia is 3 to 12 g/day.

Contraindications

Liver disease.

Pregnancy/Lactation

Avoid use. Embryonic toxicity has been reported.

Interactions

None well documented.

Adverse Reactions

P. multiflorum is widely used in Chinese medicine; however, adverse event reporting under clinical trial conditions is lacking. Hepatotoxicity has been documented.

Toxicology

Evidence of hepatic injury in humans exists; consider P. multiflorum and its extracts hepatotoxic. The plant may also be nephro-, neuro-, and embryotoxic.

Scientific Family

  • Polygonaceae (buckwheat)

Botany

P. multiflorum is native to central and southern China and is also distributed in Japan and Taiwan. It is a perennial climbing herb that can grow to 9 m in height. The plant has red stems, heart-shaped leaves, and white or pink flowers. The roots are the main plant part of interest and are harvested and dried in autumn when they are 3 to 4 years of age, but the stems and leaves are also used. Raw, wine- or steam-processed, or cured fo-ti is available in the United States.1, 2, 3, 4

History

Radix Polygoni multiflori or he shou wu is a popular Chinese tonic herb, whose usage dates back to 713 AD.2 Fo-ti appears to be a name given to the preparation for use in areas where Chinese is not the primary language.4 It is considered one of the country's great 4 herbal tonics, along with angelica, lycium, and panax, and is used to increase liver and kidney function and to cleanse the blood.3 The plant is also prescribed for symptoms of premature aging, such as gray hair, and is commonly found in hair care products in China.2, 4 It is also used to treat insomnia, weak bones, constipation, and atherosclerosis.2 Regarded as a rejuvenating plant, fo-ti has been thought to prevent aging and promote longevity. According to folklore, the older and larger roots have the most power, potentially offering immortality.2, 3, 4

Chemistry

Major chemical constituents include stilbenes, quinones, flavonoids phospholipids, and others. More than 100 chemical compounds have been identified, and analytical techniques are described.5, 6, 7, 8, 9

Chemicals of interest include the anthraquinones emodin, physcion, and rhein; stilbenes; and a tetrahydroxystilbene glucoside.7, 10, 11, 12 Minerals and vitamins in the root have also been described.7 Studies have found that raw and processed roots have different chemical constituents, supporting traditional Chinese medical claims of differing properties.5, 13, 14

Uses and Pharmacology

Extracts of P. multiflorum are not commonly used alone, but rather in combination with other herbs,5 including Buyangahuanw Pill Jiajian Fang and Qishu decoction. Clinical trials reporting on efficacy are limited.4

Aging

Animal data

A mixture including he shou wu has been studied for its effects on the glucocorticoid receptor in senile rat thymocytes.15 An effect of emoghrelin, derived from P. multiflorum, stimulated growth hormone in vitro,16 and tetrahydroxystilbene glucoside protected against the thinning of mice derma associated with aging.17 Lifespan and lipid studies of he shou wu in quails have been performed.18

Clinical studies

There are no clinical data regarding the use of P. multiflorum for antiaging effects. Purported antiaging effects mostly rely on in vitro studies of antioxidant and neuroprotective effects.5

Alopecia

Animal data

Topical application of P. multiflorum has to induced follicular keratinocyte proliferation in mice.19, 20 The inhibition of tyrosinase activity in mice melanocytes has also been demonstrated,21 and compounds isolated from P. multiflorum roots induced a greater proliferation of dermal papilla cells than minoxidil in an in vitro study.22

Clinical studies

There are no clinical data regarding the use of P. multiflorum in alopecia or hair coloring despite widespread traditional use in China for this purpose.

Cancer

Animal data

In vitro studies and limited animal data suggest P. multiflorum extracts, tetrahydroxystilbene glucoside and emodin, possess anticancer properties.5, 12, 23, 24 The focus of research into antiapoptotic activity centers on neuroprotection against degenerative disease (see CNS).

Clinical data

There are no clinical data regarding the use of P. multiflorum in cancer.

Cardiovascular/Atherosclerosis

Animal data

Emodin has demonstrated inhibitory effects on vasodilation in isolated rat aortas.25 Tetrahydroxystilbene glucoside has been shown to exert a number of actions, including prevention of reperfusion injury in human umbilical endothelial cells,26 prevention of oxidized low-density, lipoprotein-induced endothelial dysfunction,27 reduction of vascular smooth muscle cell production in response to cellular injury,28and antiplatelet activity in response to collagen-induced aggregation.29

Clinical data

There are no clinical data regarding the use of P. multiflorum in cardiovascular-related disorders.

CNS

Animal data

In vitro studies in tissues of the CNS report decreased neuroinflammation via inhibition of microglia activation,30 promotion of hippocampal synaptic plasticity,31 antioxidant effect in hippocampal and other cells,32, 33, 34, 35 and the reduction of amyloid peptide production.36 In contrast, an in vitro study using cultured mouse cortical neurons showed an extract of P. multiflorum to be neurotoxic.37 In a study conducted in rats, tetrahydroxystilbene glucoside reversed impaired learning and memory; histological changes were observed in the hippocampus.38

Clinical data

P. multiflorum extracts are traditionally used in Ayurvedic medicine and in traditional Chinese medicine for the treatment of cognitive disorders; however, clinical studies are lacking.37 One study conducted among patients with Alzheimer disease (N = 209) reported that the extract was effective; details of the methodology are unclear.39

Dyslipidemia

Animal data

Effects on triglyceride and total cholesterol regulation have been demonstrated by tetrahydroxystilbene glucoside, emodin, and physcion in mice and in vitro.40, 41, 42, 43 Raw fo-ti appeared to be more effective than processed fo-ti in 1 study.41

Clinical data

There are no clinical data regarding the use of P. multiflorum in dyslipidemia; however, both raw and cured fo-ti are used in traditional Chinese medicine for dyslipidemia.4

Other uses

In vitro studies have shown that extracts of P. multiflorum possess antioxidant properties.30, 35, 37, 44, 45, 46, 47, 48 Immunomodulatory and anti-inflammatory effects have also been reported.5 Reduction in the production of glycation end products in diabetes has been demonstrated in vitro.49

In contrast to the known hepatotoxicity of P. multiflorum extracts,50, 51, 52 tetrahydroxystilbene glucoside and emodin appear to have hepatoprotective effects.30, 32, 43, 48

Dosing

P. multiflorum is used at daily doses of 9 to 15 g of raw herb, but clinical studies are lacking. A standard dose in the Chinese Pharmacopoeia is 3 to 12 g/day.50

P. multiflorum is usually used in combination with other traditional products.4, 5

Pregnancy / Lactation

Avoid use. Embryonic toxicity has been reported.53

Interactions

Case reports are lacking. An in vitro study suggests tetrahydroxystilbene glucoside exerts an inhibitory effect on platelet aggregation.29

Adverse Reactions

P. multiflorum is widely used in Chinese medicine; however, adverse event reporting under clinical trial conditions is lacking. Hepatotoxicity has been documented.50, 51, 52 GI symptoms, including diarrhea, may be due to consuming raw or improperly processed fo-ti.4

Data collected between 2004 and 2013 among 8 US centers in the Drug-induced Liver Injury Network revealed 15.5% (130) of hepatotoxicity cases was caused by herbals and dietary supplements whereas 85% (709) were related to medications. Of the 130 related cases of liver injury related to supplements, 65% were from non-bodybuilding supplements and occurred most often in Hispanic/Latinos compared to non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent with toxicity from non-bodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the number of severe liver injury cases was significantly higher from supplements than conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, fo-ti was among the 22% (116) of the single-ingredient products.55

Toxicology

Evidence of hepatic injury in humans exists; consider P. multiflorum and its extracts hepatotoxic. The plant may also be nephro-, neuro-, and embryotoxic.

Reviews of the toxic effects, possibly dose- and duration-related, of P. multiflorum on the liver have been published. Other reviews suggest an idiopathic nature to the toxicity, with more than 400 cases reported. Hepatotoxicity is largely reversible; however, deaths have been reported.50, 51, 52 Nephrotoxicity and embryonic toxicity53 have also been reported and attributed to the quinone constituents emodin and rhein.5, 37

Tetrahydroxystilbene glucoside and emodin appear to have neuro-, nephro-, and hepatoprotective effects.30, 32, 43, 48, 54 In mice, processing the raw roots increased emodin and decreased tetrahydroxystilbene glucoside content and diminished observed toxicity.13

In rats, tetrahydroxystilbene glucoside was detected in the liver and lungs in the highest concentrations, but not in brain and testes tissues.6 Mutagenicity and toxicity to lung tissue have also been described.5

References

1. Polygonum multiflorum Thunb. USDA, NRCS. 2015. The PLANTS database (http://Plants.usda.gov, 2015). National Plant Data Team, Greensboro, NC 27401-4901 USA. 2015.
2. Chevallier A. Encyclopedia of Medicinal Plants. New York, NY: DK Publishing; 1996.
3. Reid D. Chinese Herbal Medicine. Boston, MA: Shambhala Publishing; 1994.
4. Khan I, Abourashed E. Leung's Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics. 3rd ed. Hoboken, NJ: Wiley; 2009.
5. Lin L, Ni B, Lin H, et al. Traditional usages, botany, phytochemistry, pharmacology and toxicology of Polygonum multiflorum Thunb.: A review. J Ethnopharmacol. 2015;159:158-183.25449462
6. Lv G, Lou Z, Chen S, Gu H, Shan L. Pharmacokinetics and tissue distribution of 2,3,5,4′-tetrahydroxystilbene-2-O-beta-D-glucoside from traditional chinese medicine Polygonum multiflorum following oral administration to rats. J Ethnopharmacol. 2011;137(1):449-456.21679759
7. Duke J. Handbook of Biologically Active Phytochemicals and Their Activities. Boca Raton, FL: CRC Press; 1992. http://www.ars-grin.gov/duke/. Accessed 2014.
8. Liu C, Zhang Q, Zhou Q. Assay of stilbene glucoside in Polygonum multiflorum Thunb and its process products [in Chinese]. Zhongguo Zhong Yao Za Zhi. 1991;16(8):469-472.1804184
9. Ma C, Wang, J. Comparison of phospholipids in crude drug of Polygonum multiflorum Thunb. And its processed products. Zhongguo Zhong Yao Za Zhi. 1991;16(11):662-664.1804168
10. Oerter Klein K, Janfaza M, Wong JA, Chang RJ. Estrogen bioactivity in fo-ti and other herbs used for their estrogen-like effects as determined by a recombinant cell bioassay. J Clin Endocrinol Metab. 2003;88(9):4077-4079.12970265
11. Grech JN, Li Q, Roufogalis BD, Duck CC. Novel Ca(2+)-A TPase inhibitors from the dried root tubers of Polygonium multiflorum. J Nat Prod. 1994;57(12):1682-1687.7714535
12. Sun YN, Li W, Kim JH, et al. Chemical constituents from the root of Polygonum multiflorum and their soluble epoxide hydrolase inhibitory activity [published ahead of print]. Arch Pharm Res. 2014.25413971
13. Wu X, Chen X, Huang Q, Fang D, Li G, Zhang G. Toxicity of raw and processed roots of Polygonum multiflorum. Fitoterapia. 2012;83(3):469-475.22210538
14. Liang Z, Chen H, Yu Z, Zhao Z. Comparison of raw and processed radix Polygoni Multiflori (Heshouwu) by high performance liquid chromatography and mass spectrometry. Chin Med. 2010;5:29.20704710
15. Zhao W, Jin GQ. Effect of guzhen recipe on glucocorticoid receptor in senile rat thymocyte [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1995;15(2):92-94.7787400
16. Lo YH, Chen YJ, Chung TY, et al. Emoghrelin, a unique emodin derivative in heshouwu, stimulates growth hormone secretion via activation of the ghrelin receptor. J Ethnopharmacol. 2015;159:1-8.25446595
17. Zhou X, Ge L, Yang Q, et al. Thinning of dermas with the increasing age may be against by tetrahydroxystilbene glucoside in mice. Int J Clin Exp Med. 2014;7(8):2017-2024.25232382
18. Wang W, Wang JH, Shi TR. Effect of Polygonum multiflorum on the life-span and lipid metabolism in senile Japanese quails. Zhong Xi Yi Jie He Za Zhi. 1988;8(4):223-224.3191547
19. Begum S, Gu LJ, Lee MR, et al. In vivo hair growth-stimulating effect of medicinal plant extract on BALB/c nude mice [published ahead of print]. Pharm Biol. 2015:1-6.25612775
20. Park SJ, Jin ML, An HK, et al. Emodin induces neurite outgrowth through PI3K/akt/GSK-3β-mediated signaling pathways in Neuro2a cells. Neurosci Lett. 2015;588:101-107.25562207
21. Cheung FW, Leung AW, Liu WK, Che CT. Tyrosinase inhibitory activity of a glucosylated hydroxystilbene in mouse melan-a melanocytes. J Nat Prod. 2014;77(6):1270-1274.24933607
22. Sun YN, Cui L, Li W, et al. Promotion effect of constituents from the root of Polygonum multiflorum on hair growth. Bioorg Med Chem Lett. 2013;23(17):4801-4805.23896496
23. Chen HS, Liu Y, Lin LQ, et al. Anti-proliferative effect of an extract of the root of Polygonum multiflorum Thunb. on MCF-7 human breast cancer cells and the possible mechanisms. Mol Med Rep. 2011;4(6):1313-1319.21874249
24. Horikawa K, Mohri T, Tanaka Y, Tokiwa H. Moderate inhibition of mutagenicity and carcinogenicity of benzo[a]pyren, 1,6-dinitropyrene and 3,9-dinitrofluoranthene by Chinese medicinal herbs. Mutagenesis. 1994;9(6):523-526.7854143
25. Lim KM, Kwon JH, Kim K, et al. Emodin inhibits tonic tension through suppressing PKCδ-mediated inhibition of myosin phosphatase in rat isolated thoracic aorta. Br J Pharmacol. 2014;171(18):4300-4310.24909118
26. Liu LP, Liao ZP, Yin D, et al. The protective effects of Polygonum multiflorum stilbeneglycoside preconditioning in an ischemia/reperfusion model of HUVECs. Acta Pharmacol Sin. 2010;31(4):405-412.20228828
27. Yao W, Fan W, Huang C, Zhong H, Chen X, Zhang W. Proteomic analysis for anti-atherosclerotic effect of tetrahydroxystilbene glucoside in rats. Biomed Pharmacother. 2013;67(2):140-145.23206751
28. Xu XL, Huang YJ, Ling DY, Zhang W. Inhibitory effects of 2,3,4′,5-tetrahydroxystilbene-2-O-β-D-glucoside on angiotensin II-induced proliferation of vascular smooth muscle cells. Chin J Integr Med. 2014;21(3):204-210.25078359
29. Xiang K, Liu G, Zhou YJ, et al. 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) attenuates human platelet aggregation, secretion and spreading in vitro. Thromb Res. 2014;133(2):211-217.24332167
30. Zhang JK, Yang L, Meng GL, et al. Protective effect of tetrahydroxystilbene glucoside against hydrogen peroxide-induced dysfunction and oxidative stress in osteoblastic MC3T3-E1 cells. Eur J Pharmacol. 2012;689(1-3):31-37.22683865
31. Wang T, Yang YJ, Wu PF, et al. Tetrahydroxystilbene glucoside, a plant-derived cognitive enhancer, promotes hippocampal synaptic plasticity. Eur J Pharmacol. 2011;650(1):206-214.20951128
32. Kim HN, Kim YR, Jang JY, et al. Neuroprotective effects of Polygonum multiflorum extract against glutamate-induced oxidative toxicity in HT22 hippocampal cells. J Ethnopharmacol. 2013;150(1):108-115.23973786
33. Jang JY, Kim HN, Kim YR, et al. Hexane extract from Polygonum multiflorum attenuates glutamate-induced apoptosis in primary cultured cortical neurons. J Ethnopharmacol. 2013;145(1):261-268.23164763
34. Qin R, Li X, Li G, et al. Protection by tetrahydroxystilbene glucoside against neurotoxicity induced by MPP+: the involvement of PI3K/akt pathway activation. Toxicol Lett. 2011;202(1):1-7.21237255
35. Steele ML, Fuller S, Patel M, Kersaitis C, Ooi L, Munch G. Effect of Nrf2 activators on release of glutathione, cysteinylglycine and homocysteine by human U373 astroglial cells. Redox Biol. 2013;1:441-445.24191238
36. Liu LF, Durairajan SS, Lu JH, Koo I, Li M. In vitro screening on amyloid precursor protein modulation of plants used in ayurvedic and traditional Chinese medicine for memory improvement. J Ethnopharmacol. 2012;141(2):754-760.21920424
37. Shen B, Truong J, Helliwell R, Govindaraghavan S, Sucher NJ. An in vitro study of neuroprotective properties of traditional Chinese herbal medicines thought to promote healthy ageing and longevity. BMC Complement Altern Med. 2013;13:373.24373151
38. Zhou L, Hou Y, Yang Q, et al. Tetrahydroxystilbene glucoside improves the learning and memory of amyloid-β(1-42)-injected rats and may be connected to synaptic changes in the hippocampus. Can J Physiol Pharmacol. 2012;90(11):1446-1455.23181273
39. Chen L, Huang J, Xue L. Effect of compound Polygonum multiflorum extract on Alzheimer's disease [in Chinese]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010;35(6):612-615.20622335
40. Liu C, Zhang Q, Lin J.Effect of the root of Polygonum multiflorum Thunb. And its processed products on fat accumulation in the liver of mice. Zhongguo Zhong Yao Za Zhi. 1992;17(10):595-596.1294175
41. Wang M, Zhao R, Wang W, Mao X, Yu J. Lipid regulation effects of Polygoni multiflori radix, its processed products and its major substances on steatosis human liver cell line L02. J Ethnopharmacol. 2012;139(1):287-293.22120683
42. Wang W, He Y, Lin P, et al. In vitro effects of active components of Polygonum multiflorum radix on enzymes involved in the lipid metabolism. J Ethnopharmacol. 2014;153(3):763-770.24680992
43. Li C, Cai F, Yang Y, et al. Tetrahydroxystilbene glucoside ameliorates diabetic nephropathy in rats: Involvement of SIRT1 and TGF-β1 pathway. Eur J Pharmacol. 2010;649(1-3):382-389.20854812
44. Hong CY, Lo YC, Tan FC, Wei YH, Chen CF. Astragalus membranaceus and Polygonum multiflorum protect rat heart mitochondria against lipid peroxidation. Am J Chin Med. 1994;22(1):63-70.8030620
45. Tao L, Li X, Zhang L, et al. Protective effect of tetrahydroxystilbene glucoside on 6-OHDA-induced apoptosis in PC12 cells through the ROS-NO pathway. PLoS One. 2011;6(10):e26055.21998750
46. Lv L, Cheng Y, Zheng T, Li X, Zhai R. Purification, antioxidant activity and antiglycation of polysaccharides from Polygonum multiflorum Thunb. Carbohydr Polym. 2014;99:765-773.24274568
47. Li X, Li Y, Chen J, et al. Tetrahydroxystilbene glucoside attenuates MPP+-induced apoptosis in PC12 cells by inhibiting ROS generation and modulating JNK activation. Neurosci Lett. 2010;483(1):1-5.20643188
48. Lee BH, Huang YY, Duh PD, Wu SC. Hepatoprotection of emodin and Polygonum multiflorum against CCl(4)-induced liver injury. Pharm Biol. 2012;50(3):351-359.22103790
49. Lv L, Shao X, Wang L, Huang D, Ho CT, Sang S. Stilbene glucoside from Polygonum multiflorum Thunb.: A novel natural inhibitor of advanced glycation end product formation by trapping of methylglyoxal. J Agric Food Chem. 2010;58(4):2239-2245.20104848
50. Dong H, Slain D, Cheng J, Ma W, Liang W. Eighteen cases of liver injury following ingestion of Polygonum multiflorum. Complement Ther Med. 2014;22(1):70-74.24559819
51. Lei X, Chen J, Ren J, et al. Liver damage associated with Polygonum multiflorum Thunb.: A systematic review of case reports and case series. Evid Based Complement Alternat Med. 2015;2015:459749.25648693
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54. Sun FL, Zhang L, Zhang RY, Li L. Tetrahydroxystilbene glucoside protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity. Eur J Pharmacol. 2011;660(2-3):283-290.21497157
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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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