Fo-Ti

Background & General Info

Polygonum multiflorum, a member of Polygonaceae family, is otherwise known as fo-ti in North America. It is a well-celebrated perennial herb in several East Asian countries, especially China, where it is integrated in complex formulas of herbs or is traditionally used as a single herb. ^[1] The root of the plant is called He Shou Wu in Chinese Pinyin. ^[1]

Fo-Ti - Botany

The briquette or irregularly spindle roots of Polygonum multiflorum can reach a length of up to 6–15 cm and appear reddish brown and uneven with shallow grooves on the outside. They seem shrunken and have transverse lenticel-like protrusion and fine rootlet scars. The pale yellowish-brown or reddish-brown fracture is starchy, with a dense, compact texture. ^[2]

Fo-Ti - History & Traditional Use

The Kaibao Bencao, the material medica of the Kaibao period published by the imperial court of the Song Dynasty (973–974 A.D.), provided one of the earliest accounts of Polygonum multiflorum as a Chinese herb. Several years ago as early as A.D. 812, Polygonum multiflorum was documented as an extremely tonic medicine that could “benefit for the essence, strong your spirits, protect your beauty, black your hair, and extend your life,” and in the Compendium of Materia Medica that dated back to A.D. 1578, the plant had been recorded to “benefit the essence, kidney, spleen, bones and hair as a tonic traditional Chinese medicine”. ^[3]

The Chinese Pharmacopoeia categorizes the medicinal decoction of Polygonum multiflorum roots into two forms, that is, the raw state, or the natural root, and its processed form, or the radix polygoni multiflori preparata, which is traditionally boiled in black bean liquid. The raw roots of the plant are prescribed for detoxification, eradication of carbuncle, prevention of malaria, and relaxation of bowels, whereas the processed roots are used to nourish the liver and kidney, supplement essence and blood, blacken the hair, fortify the bones and muscles, get rid of dampness, and diminish amounts of lipids. ^[1]

Fo-Ti - Herbal Uses

An increasing number of pharmacological studies have been conducted that elucidated the benefits of fo-ti or Polygonum multiflorum in the treatment of a range of diseases and medical conditions, including liver injury, cancer, diabetes, alopecia, atherosclerosis, and neurodegenerative disorders. ^[4] The Shou-Wu-Pian, a popular product containing dried roots of Polygonum multiflorum, is advertised and taken as an antiaging agent with antioxidative activities, a tonic for dizziness with tinnitus, and an effective remedy for premature graying of hair, lumbago, spermatorrhea, leucorrhea, and constipation. ^[1] In East Asian countries, Polygonum multiflorum is also traditionally used as treatment of baldness and hair loss. ^[5]

Fo-Ti - Constituents / Active Components

Choi et al. (2007) isolated three anthraquinones from the methanolic extract of fo-ti roots, namely, physcion, emodin, and questin, which were all Cdc25B phosphatase inhibitors, with IC50 values of 62.5, 30, and 34 μg/mL, respectively. ^[6] Hui et al. (2008) had isolated and identified 13 compounds from the plant, namely, chrysophanol, physcion, emodin, aloeemodin, rhein, physcion-8-O-beta-D-glucoside, emodin-8-O-beta-D-glucoside, 2,3,5,4'-tetrahydroxy-stibene-2-O-beta-D-glucoside, noreugenin, apigenin, daucosterol, beta-sitosterol, and stearic acid. ^[7]

Fo-Ti - Medicinal / Scientific Research

Anticancer:

Emodin and questin, which are two of three anthraquinones isolated in the methanolic extract from the roots of Polygonum multiflorum in the study of Choi et al. (2007), have both been observed to strongly hinder the growth of SW620 human colon cancer cells with GI50 values of 6.1 and 0.9 μg/mL, respectively. ^[6] An earlier study investigating the mutagenic and carcinogenic activities of six Chinese medicinal herbs against benzo[a]pyrene (B[a]P), 1,6-dinitropyrene (1,6-diNP), and 3,9-dinitrofluoranthene (3,9-diNF) had confirmed the ability of fo-ti extract to considerably diminish tumor incidence. In an in vitro system, ethyl acetate soluble fraction of Polygonum multiflorum displayed substantial and dose-dependent antimutagenic action against B[a]P. Moreover, epigallocatechin, epigallocatechin gallate, epicatechin gallate, and tannic acid, which are the major components of the extract, strongly suppressed the mutagenicity of B[a]P at a concentration of 2.5 μg/plate in Salmonella typhimurium TA98 with S9 mix. ^[8]

Kwon et al. (2009) had also demonstrated the inhibition of farnesyl protein transferase by methanol extract from Polygonum multiflorum roots. A class of experimental cancer drugs called farnesyl protein transferase inhibitors has been proposed as potential cancer chemopreventives due to their suppression of the previously mentioned enzyme, leading to the prevention of proper functioning of Ras proteins that are usually abnormally active in cancer, and their suppression of Ras-dependent proliferative activity in cancerous and precancerous lesions. Employing bioassay-guided fractionation, the study isolated two anthraquinone glycosides from the methanol extract that dose-dependently inhibited farnesyl protein transferase. ^[9]

Antibacterial:

A 2008 assessment of extracts from Chinese herbs had confirmed the in vitro antibacterial activity of Polygonum multiflorum against methicillin-resistant Staphylococcus aureus. Among the 19 plant extracts wherein bioassay-guided phytochemical analysis was performed, Polygonum multiflorum was one of the most active in terms of antimicrobial effect, with a minimal inhibitory concentration (MIC) of ≤1.43 mg/mL. ^[10]

Neuroprotective:

Fo-ti extract has been found to confer neuroprotection by lessening activation of extracellular regulated kinase (ERK) and p38 and increasing activation of CREB under oxidative stress conditions, making it a suitable therapeutic intervention for ailments characterized by oxidative neuronal death. In the study of Kim et al. (2013), neuroprotective property was observed for an ethyl acetate extract derived from Polygonum multiflorum, whose pretreatment resulted in a significant reduction in glutamate-induced neurotoxicity in HT22 hippocampal cells and in a drastic inhibition of glutamate-induced apoptotic and necrotic neuronal death. Pretreatment with fo-ti ethyl acetate extract led to a marked recovery of pro-calpain I and active form of striatal-enriched protein tyrosine phosphatase (STEP). ^[11]

A 2006 study in rats demonstrated the protective activity of fo-ti water extract against cognitive deficits triggered by intracerebroventricular injection of amyloid beta peptide 25–35 (Abeta25–35) at a dose of 10 μg. Results from this study indicated that consumption of fo-ti water extract notably improved the cognitive deficits induced by Abeta25–35 accumulation and attenuated the increase of levels of thiobarbituric acid reactive substances in the brain due to Abeta25–35. Treated rats also showed an increase in glutathione peroxidase activity and lower acetylcholinesterase activity in the brain and serum. ^[12]

Memory And Learning:

Study findings of Chan, Cheng, and Wang (2002) indicated that dietary supplementation with either Polygonum multiflorum ethanol or water extracts decreases pathological alterations in the brain and supports learning and memory. The study involved four groups of senescence-accelerated mice that were fed for 18 weeks with baseline casein diet and test diets supplemented with 50% ethanol, 95% ethanol, or water extracts derived from Polygonum multiflorum. Mice whose diets were supplemented with Polygonum multiflorum extracts were characterized by better active shuttle avoidance response, fewer vacuole numbers, less amount of lipofuscin in the hippocampus, and lower MDA concentrations in the brain, but those taking 50% and 95% ethanol Polygonum multiflorum extracts appeared to have lower lipofuscin percentages and MDA concentrations and higher total thiol concentrations than mice fed with the water extract. Moreover, mice fed with 50% ethanol extract displayed significantly reduced levels of total cholesterol and triglyceride. ^[13]

Hair Growth:

In a 2015 research where C57BL/6J mice were employed to evaluate the hair growth promotion activity of Polygonum multiflorum radix and its preparation, groups orally treated with fo-ti radix manifested higher hair covered skin ratio (100 ± 0.00%) than groups treated orally with the preparation (48–88%), but both oral administration of Polygonum multiflorum radix and topically provided Polygonum multiflorum preparation displayed hair growth promotion activities. It appears that the former promotes hair growth through mediation of expression of FGF-7, whereas the latter encourages hair growth by stimulating SHH expression. ^[3] An earlier 2011 study that topically applied Polygonum multiflorum extract on shaved dorsal skin of telogenic C57BL6/N mice showed that the extract promoted hair growth via induction of the anagen phase. Groups treated with the Polygonum multiflorum extract exhibited an increase in the number and size of hair follicles, indicating anagen phase induction. Based on immunohistochemical analysis, β-catenin and Shh were induced earlier in the group treated with the extract compared with the control group. ^[5]

Fo-Ti - Contraindications, Interactions, And Safety

Banarova, Koller, and Payer (2012) reported a case of toxic hepatitis due to 2-month ingestion of pills containing fo-ti extract in a 33-year old female who manifested clinical signs of nausea and jaundice and laboratory signs of hepatocellular damage. Discontinued use of fo-ti pills had led to early recovery, and international scoring system of causality between Polygonum multiflorum and hepatotoxicity and resemblance of findings with other reports from the literature have established the causality relation between hepatocellular damage and fo-ti extract ingestion. ^[14] A 2015 systematic review covered 450 case reports and case series about liver damage related to raw and processed Polygonum multiflorum preparations from six medical databases and concluded that fo-ti and its various formulations can indeed cause liver toxicity and damage at different degrees and even death, which are associated with long-term and overdose use of drugs. Symptoms of liver damage, which can persist for almost a month, consist of jaundice, fatigue, anorexia, and yellow or tawny urine. Luckily, such liver damage is reversible and cured when actively treated. ^[1]

References:

[1] X. Lei, J. Chen, J. Ren and e. al., "Liver damage associated with Polygonum multiflorum Thunb.: A systematic review of case reports and case series," Evidence-Based Complementary and Alternative Medicine : eCAM, vol. 2015, p. 459749, 2015.

[2] "Polygonum multiflorum Root," U.S. Pharmacopeial Convention Herbal Medicines Compendium, 2017. https://hmc.usp.org/monographs/polygonum-multiflorum-root-1-0

[3] Y. Li, M. Han, P. Lin and e. al., "Hair growth promotion activity and its mechanism of Polygonum multiflorum," Evidence-Based Complementary and Alternative Medicine, vol. 2015, p. 10, 2015.

[4] G.-A. Bounda and Y. Feng, "Review of clinical studies of Polygonum multiflorum Thunb. and its isolated bioactive compounds," Pharmacognosy Research, vol. 7, no. 3, p. 225–236, 2015.

[5] H. Park, N. Zhang and D. Park, "Topical application of Polygonum multiflorum extract induces hair growth of resting hair follicles through upregulating Shh and β-catenin expression in C57BL/6 mice," Journal of Ethnopharmacology, vol. 135, no. 2, p. 369–375, 2011.

[6] S. Choi, J. Kim, N. Sung and e. al., "Anthraquinones, Cdc25B phosphatase inhibitors, isolated from the roots of Polygonum multiflorum Thunb.," Natural Product Research, vol. 21, no. 6, p. 487–493, 2007.

[7] T. Hui, Y. Xue, Q. Zhang and e. al., "Studies on chemical constituents from rattan of Polygonum multiflorum," Journal of Chinese Medicinal Materials, vol. 31, no. 8, p. 1163–1165, 2008.

[8] K. Horikawa, T. Mohri, Y. Tanaka and H. Tokiwa, "Moderate inhibition of mutagenicity and carcinogenicity of benzo[a]pyrene, 1,6-dinitropyrene and 3,9-dinitrofluoranthene by Chinese medicinal herbs," Mutagenesis, vol. 9, no. 6, p. 523–526, 1994.

[9] B. Kwon, S. Kim, N. Baek and e. al., "Farnesyl protein transferase inhibitory components of Polygonum multiflorum," Archives of Pharmacal Research, vol. 32, no. 4, p. 495–499, 2009.

[10] G. Zuo, G. Wang, Y. Zhao, G. Xu, X. Hao, J. Han and Q. Zhao, "Screening of Chinese medicinal plants for inhibition against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA)," Journal of Ethnopharmacology, vol. 120, no. 2, p. 287–290, 2008.

[11] H. Kim, Y. Kim, J. Jang and e. al., "Neuroprotective effects of Polygonum multiflorum extract against glutamate-induced oxidative toxicity in HT22 hippocampal cells," Journal of Ethnopharmacology, vol. 150, no. 1, p. 108–115, 2013.

[12] M. Um, W. Choi, J. Aan, S. Kim and T. Ha, "Protective effect of Polygonum multiflorum Thunb on amyloid beta-peptide 25-35 induced cognitive deficits in mice," Journal of Ethnopharmacology, vol. 104, no. 1–2, p. 144–148, 2006.

[13] Y. Chan, F. Cheng and M. Wang, "Beneficial effects of different Polygonum multiflorum Thunb. extracts on memory and hippocampus morphology," Journal of Nutritional Science and Vitaminology (Tokyo), vol. 48, no. 6, p. 491–497, 2002.

[14] A. Banarova, T. Koller and J. Payer, "Toxic hepatitis induced by Polygonum multiflorum," Vnitr̆ní lékar̆ství, vol. 58, no. 12, p. 958–962, 2012.

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