Polygonum

Polygonum: A Comprehensive Reference on Botanical Identity, Traditional Use, Active Compounds, and Scientific Evidence

1. Identity and Botanical Classification

The genus Polygonum, belonging to the family Polygonaceae (the buckwheat or knotweed family), encompasses a large and taxonomically complex group of flowering plants. In dietary supplement and ethnopharmacological contexts, two species within and formerly within this genus are of primary medical and commercial importance: Polygonum multiflorum Thunb. (Chinese climbing knotweed, He Shou Wu, Fo-Ti) and Polygonum cuspidatum Siebold & Zucc. (Japanese knotweed, Hu Zhang). Because these two species are the principal subjects of pharmacological research and supplement use, this article addresses both, distinguishing between them throughout.

1.1 Polygonum multiflorum (He Shou Wu / Fo-Ti)

Polygonum multiflorum (synonyms: Fallopia multiflora, Reynoutria multiflora, Pleuropterus multiflorus) is a species of flowering plant in the buckwheat family Polygonaceae, native to central and southern China, Hainan, Taiwan, Vietnam, and Thailand. It is known by the English common names tuber fleeceflower and Chinese (climbing) knotweed, and is known as he shou wu (何首烏) in China and East Asia. Another common name for the species is fo-ti, which is technically considered a misnomer.

Polygonum multiflorum Thunb. (PM), also known as He Shou Wu (HSW), is a perennial vine of the Polygonaceae family. The plant is a herbaceous perennial vine growing to 2–4 m (6 ft 7 in – 13 ft 1 in) tall from a woody tuber. The primary medicinal part is the dried tuberous root.

Polygonum multiflorum was first described by Thunberg in 1784 and was considered to belong to the genus Polygonum. In 1978, Polygonum multiflorum was placed in the genus Fallopia Adanson by Haraldson and renamed Fallopia multiflora. Despite this reclassification, the name Polygonum multiflorum remains widely used in clinical, pharmacological, and regulatory literature.

There are two forms of PM decoctions in the Chinese Pharmacopoeia (2015): Raw Radix P. multiflorum (RPM) and P. multiflorum Praeparata (PMP). According to Chinese medicine theory, raw Radix Polygoni Multiflori (R-RPM) counteracts toxicity, cures carbuncles, and relaxes the bowels, whereas processed Radix Polygoni Multiflori (P-RPM) replenishes the liver and kidney with vital essence and blood, blackens the hair, and strengthens the tendons and bones.

P. multiflorum is also known as Shou Wu Pian, He Shou Pian, Fo-Ti, and Chinese knotweed.

1.2 Polygonum cuspidatum (Japanese Knotweed / Hu Zhang)

Polygonum cuspidatum Sieb. et Zucc., a traditional, popular Chinese medicinal herb, is widely distributed in Southern China and Japan. The dried root of Polygonum cuspidatum Sieb. et Zucc. (also known as "Hu Zhang" in Chinese) is one of the medicinal herbs listed in the Pharmacopoeia of the People's Republic of China. Hu Zhang is widely distributed in the world and can be found in Asia and North America; it is used as folk medicine in countries such as Japan and Korea.

P. cuspidatum is also known by the synonymous names Fallopia japonica and Reynoutria japonica in current botanical nomenclature. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a natural polyphenolic compound that exists in Polygonum cuspidatum, grapes, peanuts, and berries, as well as their manufactured products, especially red wine. The plant is commercially grown as a major source for resveratrol extraction for the supplement industry.

2. Natural Source and Common Forms/Preparations

2.1 Parts Used

• P. multiflorum: The dried root tuber (Radix Polygoni Multiflori) is the principal medicinal part. The stem (Caulis Polygoni Multiflori, Ye Jiao Teng) is also used in traditional practice, predominantly as a sedative.
• P. cuspidatum: The dried root (rhizome) is the primary part used for medicinal and supplement purposes.

2.2 Processing and Preparations

Proper pharmaceutical processing may reduce toxicity or side effects, potentiate the beneficial effects, change the pharmacological properties, preserve active constituents, facilitate administration, improve flavor, or correct unpleasant taste. In China, the processing methods for Radix Polygoni Multiflori have been practiced since the Tang dynasty and are documented in the Chinese pharmacopoeia.

Common forms of P. multiflorum preparations include:

• Decoctions (water-based teas) from raw or processed root
• Standardized ethanolic or aqueous extracts in capsule or tablet form
• PM soaked in wine after steaming, PM dried and ground into powder after steaming, oral liquids containing PM, capsules containing PM, and Shou Wu tea

Common forms of P. cuspidatum preparations include standardized root extracts standardized to a percentage of trans-resveratrol, tinctures, and powdered root capsules. Japan has resveratrol extracted from Polygonum cuspidatum and other plants available as functional food additives. Extracts can be prepared by pressurized liquid extraction (PLE), maceration, ultrasound-assisted solvent extraction (UASE), and sea sand disruption method (SSDM) using different extractants such as methanol, methanol–water mixture, and water.

The chemical constituents in P. multiflorum change after processing, and novel components can be created. The combined anthraquinone content decreases with increased processing. The content of free anthraquinones, such as emodin and physcion, increases with prolonged processing time.

3. Traditional and Historical Use

3.1 Polygonum multiflorum in Traditional Chinese Medicine

First documented in "Kai Bao Ben Cao," HSW has been a staple in traditional Chinese medicine for centuries, treating a range of ailments including sores, age-related conditions, and anemia. The root tuber of this plant was recorded in the herbal Kaibao Bencao published by the imperial court of the Song Dynasty (973–974 A.D.). It is generally referred to as Shou Wu Pian or Ho-Shou-Wu.

Polygonum multiflorum is one of the most popular traditional Chinese medicines and is an ingredient in many medicines and prescriptions. It has been widely used to treat various diseases that have been commonly associated with aging for many centuries in China.

It is traditionally valued and reported for hair-blacking, liver- and kidney-tonifying, and anti-aging effects. The herb also appears to have been used in the treatment of premature greying of hair, lumbago, spermatorrhea, leucorrhea, and constipation.

There are two forms of PM decoctions in the Chinese Pharmacopoeia (2015). While RPM contributes to detoxification and bowel relaxation, PMP tonifies the liver and kidney, benefits essence of blood and black beard, and relieves hyperlipidemia, fatty liver, and osteoporosis.

Heshouwu has also been recorded in the Korean and the Japanese Pharmacopoeia and is commonly used as a traditional Chinese medicine for the treatment of alopecia and allergies in Europe, America, and Australia.

3.2 Polygonum cuspidatum in Traditional Chinese and Japanese Medicine

The root of Polygonum cuspidatum has been used in the treatment of inflammation, female disorders, infection, jaundice, skin burns, and hyperlipemia diseases. Hu Zhang is frequently used as a hepatoprotective and cholagogic drug in TCM. Its effects on hypertension, hyperlipidemia, and cardiovascular and neurodegenerative diseases have also been intensively investigated, both experimentally and clinically.

In China, Hu Zhang is usually used in combination with other TCM herbs. The plant also has a history of use in Japan and Korea, with a traditional use record spanning approximately two thousand years in East Asian medicine.

4. Key Constituents and Active Compounds

4.1 Chemical Composition of Polygonum multiflorum

More than 103 components are isolated and characterized in PM, including flavonoids, phospholipids, quinones, stilbenes, etc.

The principal chemical classes and individual compounds include:

• Stilbenes (characteristic components): TSG (2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside), polydatin, resveratrol, rhaponiticin, and cis-TSG. Among them, stilbene glycosides such as THSG and cis-2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside (cis-THSG) are the most abundant, accounting for approximately 1.00% of the total concentration of compounds in PM.
• Anthraquinones (quinones): Quinones are the other characteristic components in Polygonum multiflorum. Quinones and their derivatives have been isolated and identified, and most of them are anthraquinones. The predominant anthraquinones are emodin-type anthraquinones, including emodin, aloe-emodin, chrysophanol, physcion, and rhein, among others.
• Flavonoids: Catechin, epicatechin, quercetin, hyperin, rutin, astragalin, proanthocyanidin B1, and proanthocyanidin B2.
• Phospholipids and other compounds: Other compounds isolated include physcion, apigenin, hyperoside, rutin, vitexin, beta-amyrin, beta-sitosterol, and daucosterol.

2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG), the primary bioactive component of Polygonum multiflorum Thunb. (commonly known as Fallopia multiflora Thunb., He shou wu, Fo-ti, or Polygoni multiflori radix), has emerged as a promising agent for combating aging and age-related diseases. TSG was first documented in the Pharmacopoeia of China (1963) as the primary quality control marker.

4.2 Chemical Composition of Polygonum cuspidatum

Currently, over 67 compounds from the root of P. cuspidatum have been isolated and identified; they include quinones, stilbenes, flavonoids, coumarins, lignans, and others.

• Stilbenes: Resveratrol and its precursor, polydatin, are two of the most important active ingredients in Polygonum cuspidatum.
• Anthraquinones: Stilbenes including resveratrol, polydatin, and anthraquinones such as emodin and its glycoside are the major compounds in Hu Zhang.
• Flavonoids: Flavonoids such as quercetin and (+)-catechin are also present.
• Quality markers: At present, emodin and polydatin are used as the marker compounds to characterize the quality of this plant in the Pharmacopoeia of the People's Republic of China.

5. Mechanisms of Action

5.1 TSG (from P. multiflorum)

2,3,4′,5-tetrahydroxystilbene-2-O-β-D-glucoside (TSG, C₂₀H₂₂O₉) is the main and unique active ingredient isolated from Polygonum multiflorum Thunb., which has extensive pharmacological activities. Modern pharmacological studies have confirmed that TSG exhibits significant activities in treating various diseases, including inflammatory diseases, neurodegenerative diseases, cardiovascular diseases, hepatic steatosis, osteoporosis, depression, and diabetic nephropathy.

Mechanistically, TSG alleviates oxidative stress, inflammation, and apoptosis while enhancing mitophagy, mitochondrial function, telomerase activity, and epigenetic regulation.

Additional documented mechanisms include:

• TSG has protective effects against cerebral ischemia by modulation of JNK, SIRT1, and NF-κB pathways.
• TSG mediates antagonistic effects on oxidation of lipoprotein, proliferation, and decrease of NO content of coronary arterial smooth muscle cells, which partially explains the antiatherosclerosis mechanism of Polygonum multiflorum.

5.2 Resveratrol (from P. cuspidatum and P. multiflorum)

Resveratrol is a pharmacologically active compound that interacts with multiple targets in a variety of cardiovascular disease models to exert protective effects or induce a reduction in cardiovascular risk parameters. Resveratrol exists in cis- and trans-configurations, of which trans-resveratrol is the principal biologically active form.

5.3 Anthraquinones (Emodin and Related Compounds)

The active components of Polygonum multiflorum are believed to be anthraquinones including chrysophanol, emodin, and rhein. Anthraquinones may account for its effect on constipation but may also account for its hepatotoxicity.

Research has indicated that lipid-lowering effects include significant decreases in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG). The key enzymes involved in lipid metabolism — 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) — are generally reduced after oral administration, consistent with the transcription levels of their target genes.

5.4 Stilbenes and Antioxidant Activity

A study proved that P. multiflorum can exhibit antioxidative activity, mainly due to its flavonoid and phenolic acid constituents. Stilbenes are significant non-flavonoid phytochemicals with a polyphenolic structure. Stilbenes can be used as medicine for their anti-oxidant, anti-proliferation, and anti-inflammatory properties.

6. Scientific Evidence by Area of Use

6.1 Aging and Anti-Aging (TSG / P. multiflorum)

Evidence level: Predominantly preclinical (animal and in vitro); systematic review of these preclinical findings available; human clinical data very limited.

Current preclinical evidence demonstrates that TSG exhibits comprehensive anti-aging effects, including lifespan extension, neuroprotection (e.g., ameliorating Alzheimer's and Parkinson's diseases), cardiovascular protection (e.g., reducing atherosclerosis and hypertension), delay of gonadal aging, reduction in bone loss (e.g., mitigating osteoporosis), and promotion of hair regrowth.

A 2015 study using the model organism Caenorhabditis elegans demonstrated lifespan extension and stress resistance with TSG, but these findings have not been replicated in human clinical trials. Modern pharmacological studies have demonstrated that TSG exhibits considerable potential in mitigating aging and age-related diseases, but the evidence base remains primarily preclinical.

6.2 Neurodegenerative Disease (Alzheimer's Disease, Parkinson's Disease)

Evidence level: Preclinical evidence moderate; human clinical data very limited and preliminary.

Therapeutic potential of Polygonum multiflorum has been demonstrated in conditions like Alzheimer's disease and Parkinson's disease, which is attributed to the presence of various stilbenes, quinones, flavonoids, phospholipids, and other compounds in the drug.

Chen et al. have investigated the therapeutic activity of PM in Alzheimer's disease (AD) through a clinical trial. However, the body of human clinical evidence remains narrow. Various clinical study articles have been retrieved providing information relevant to pharmacokinetics-pharmacodynamics analysis, sleep disorders, dyslipidemia treatment, and neurodegenerative diseases, but larger, well-controlled human trials in neurodegenerative disease are absent from the published literature as of the time of the most recent reviews.

Modern pharmacological studies have shown that TSG extracted from Polygonum multiflorum has antiaging, lipid-lowering, and neuroprotective effects. In animal models, TSG has demonstrated protective effects in cerebral ischemia/reperfusion injury, but these findings have not been confirmed in human clinical trials.

6.3 Hyperlipidemia / Dyslipidemia

Evidence level: Preliminary; one small clinical study reported; mechanism supported by preclinical data.

Several clinical studies have been conducted to evaluate the traditional therapeutic claims including anti-inflammatory bioactivity, dyslipidemia, sleep disorders, and neurodegenerative disease. PM was significantly tested for the treatment of hyperlipidemia in a clinical study that enrolled 50 patients. The findings demonstrated that the lipid-lowering effect may be related to its regulating action of the genes involved in cholesterol synthesis and lipoprotein metabolism.

This represents limited clinical evidence — a single small-scale observational study. The lipid-lowering mechanism has more extensive support from preclinical research: results indicated that basal plasma lipids, such as LDL-C, total cholesterol, and triglycerides, were significantly decreased in RPM treatment groups compared with the model group. The key enzymes HMGR, FAS, and ACC in plasma were generally reduced after oral administration. Robust, placebo-controlled human clinical trials specifically for P. multiflorum's lipid-lowering effects remain lacking.

6.4 Hair Growth and Hair Color

Evidence level: Traditional use well-documented; modern evidence primarily preclinical.

PM is traditionally valued and reported for hair-blacking, liver- and kidney-tonifying, and anti-aging effects. Several in vitro and animal studies have investigated the hair growth-promoting constituents from the root of P. multiflorum, but no large controlled human clinical trials have confirmed efficacy for hair blackening or regrowth. TSG has been identified as contributing to promotion of hair regrowth in preclinical models.

6.5 Antioxidant Activity

Evidence level: In vitro evidence robust; human clinical significance not established.

Japanese knotweed root (Polygonum cuspidatum) is a rich source of resveratrol, and the examined extracts have been shown to have antioxidant properties. TSG is a potent antioxidant; Chen et al. and Ryu et al. investigated the antioxidant activity of compounds isolated from Polygonum multiflorum (DPPH assay), showing TSG as an active constituent.

6.6 Cardiovascular Effects

Evidence level: Preclinical evidence present; one small human study for anti-inflammatory effects of P. cuspidatum extract.

Pharmacological research and clinical studies have indicated that Polygonum cuspidatum extraction and its major compounds possess anti-inflammatory, antivirus, antimicrobial, neuroprotective, and cardioprotective activities.

In one clinical study, an oral extract of P. cuspidatum 200 mg containing resveratrol 40 mg over 6 weeks was used for anti-inflammatory effect. This study (Ghanim et al., 2010, J Clin Endocrinol Metab) demonstrated suppressive effects on inflammatory markers and reactive oxygen species. However, this was a small-scale study, and broader cardiovascular endpoint trials have not been conducted with P. cuspidatum extracts specifically.

6.7 Antitumor Activity

Evidence level: Predominantly in vitro and animal; no established human clinical evidence.

A large number of studies have demonstrated that Polygonum cuspidatum and its active components like resveratrol show antitumor activities. The purpose of one review was to summarize the research progress of Polygonum cuspidatum and its active components in tumor diseases and provide theoretical basis for further scientific experiments and clinical applications.

Resveratrol has been identified as trans- and cis-resveratrol from P. cuspidatum and could specifically inhibit proliferation of many cancer cells but not human normal liver cells in in vitro models. These findings have not been translated into confirmed human clinical anti-cancer outcomes.

6.8 Anti-inflammatory Effects

Evidence level: In vitro and animal evidence well-documented; one human study for P. cuspidatum extract.

Pharmacological research has indicated that Polygonum cuspidatum extraction and its major compounds possess anti-inflammatory, antivirus, and antimicrobial activities. The published human evidence for anti-inflammatory action relates primarily to the resveratrol component derived from P. cuspidatum, notably the 2010 Ghanim et al. study referenced above.

6.9 Antibacterial and Antimicrobial Activity (P. cuspidatum)

Evidence level: In vitro only; no controlled human clinical trials.

Japanese knotweed has demonstrated antibacterial, anti-borrelia, and anti-inflammatory activity in vitro. A review of several studies found evidence for antitumor, neuroprotective, and cardioprotective effects in animals, but no human clinical studies have occurred to date. Insufficient safety data exists for Japanese knotweed due to the lack of clinical data, but a human study of trans-resveratrol showed minimal toxicity with some gastrointestinal upset.

6.10 Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)

Evidence level: Preclinical only.

PM has been proven to remedy mitochondria and relieve MAFLD in animal models, but the main pharmacodynamic ingredients for mitigating MAFLD remained unclear as of recent investigation. PM restored mitochondrial structure and function and alleviated MAFLD, which may be associated with the remedy of oxidative stress and energy production in these preclinical studies.

7. Body Systems and Health Areas Associated with Polygonum

• Nervous system: Neuroprotective effects have been demonstrated in pre-clinical and clinical practice.
• Cardiovascular system: Anti-atherosclerotic, lipid-lowering, and cardioprotective activities have been studied.
• Liver and kidney (TCM): Tonification of liver and kidney is a primary traditional indication for processed P. multiflorum.
• Immune system: Immunomodulatory activity has been reported in preclinical research.
• Musculoskeletal system: Potential benefits in osteoporosis have been identified in preclinical studies with TSG.
• Skin and hair: Traditional and some preclinical evidence for hair growth promotion and hair blackening.
• Gastrointestinal system: Laxative and bowel-relaxing effects attributed to anthraquinone content.

8. Dosage Forms and Reported Dosages

Clinical evidence on which to base dosing guidelines is limited. The following dosages are drawn directly from identified studies and reports:

• P. cuspidatum extract (anti-inflammatory clinical study): One clinical study used an oral extract of P. cuspidatum 200 mg containing resveratrol 40 mg over 6 weeks.
• P. multiflorum (hyperlipidemia clinical study): PM was significantly tested for the treatment of hyperlipidemia in a clinical study that enrolled 50 patients, though specific dose details from this study are not fully available in the published secondary literature reviewed.
• Pharmacokinetic changes after processing: A study evaluated the pharmacokinetic behaviors of typical constituents of different types of processed Polygonum multiflorum after oral administration in rats by LC-MS/MS. The results showed that the bioavailability of gallic acid improved, and the absorption of TSG, polydatin, and emodin from the processed product in rats was reduced compared with that obtained with the raw product.

Note: Doses cited in preclinical studies (animal models) and doses that appear only on commercial supplement or non-peer-reviewed sources are excluded per the sourcing standards of this article.

9. Safety Considerations and Drug Interactions

9.1 Hepatotoxicity of Polygonum multiflorum — The Central Safety Issue

Polygonum multiflorum has been implicated in numerous reports of clinically apparent acute liver injury which can be severe and even fatal.

The growing body of case reports has strengthened the association between Polygonum multiflorum and acute hepatitis over the last decade. Case reports have documented both cholestatic and hepatocellular patterns to liver injury. They have also documented liver injury associated with different forms of Polygonum multiflorum in tea, liquor, and powder form.

A published case series reports 25 patients diagnosed with toxic hepatitis following ingestion of Polygonum multiflorum Thunb. Twenty-five patients (median age 48 years [24 to 65 years]; M:F=18:7) with suspected P. multiflorum Thunb-induced liver injury were admitted between 2007 and 2009.

The ingestion of PM has been reported to lead to liver injury in many populations, including the general population and people with hair loss, white hair, vitiligo, itchy skin, high blood pressure, coronary heart disease, and high cholesterol. The clinical features of liver injury that result from the ingestion of PM or its preparations include nausea, vomiting, diarrhea, abdominal pain, nervousness, restlessness, difficulty breathing, upper gastrointestinal bleeding, and hybrid or cholestasis hepatitis.

9.2 Immunological Mechanism and Genetic Risk Factor

According to clinical and experimental studies, P. multiflorum-induced liver injury (PM-DILI) is considered to be immune-mediated idiosyncratic liver injury, but the role of immune response and the underlying mechanisms are not completely elucidated. Previous studies focused on the direct toxicity of PM-DILI by using animal models with intrinsic drug-induced liver injury (DILI). However, most epidemiological and clinical evidence demonstrate that PM-DILI is immune-mediated idiosyncratic liver injury.

The HLA allele B*35:01 appears to be a major risk factor for liver injury from Polygonum multiflorum, suggesting that the injury is immunologically mediated. Use of single-nucleotide polymorphisms identified HLA-B*35:01 to be associated with 73 cases of Polygonum multiflorum hepatotoxicity [allele frequency 0.41] compared to 118 cases of other drug-induced liver injury [0.12] and to Han population controls [0.027].

As one of the HLA-associated forms of DILI, the mechanism of PM-DILI is associated with the interaction between antigen-presenting cells (APCs) and T cells. After the metabolism of toxic components in the liver, the metabolites can be taken by dendritic cells (DCs), forming adducts covalently with self-proteins, processing in the endoplasmic reticulum, triggering the maturation of DCs. HLA-B*35:01 molecules then present the adducts at the surface of cells, waiting for the activation of CD8+ T cells by interacting with T cell receptors (TCRs).

9.3 Candidate Hepatotoxic Compounds

The components of PM responsible for the reported hepatotoxic effects have not yet been identified. Moreover, many of the reports are contradictory, while studies on the mechanism involved in PM-induced liver damage are not comprehensive.

The mechanism of hepatotoxicity of Polygonum multiflorum is not known, but the injury is usually attributed to the anthraquinones (such as emodin) which are major constituents. In a single report, the major compound identified in the recovered tablets was a stilbene glycoside, tetrahydroxystilbene-glucopyranoside.

The hepatotoxic compound responsible for Polygonum multiflorum-induced liver injury is unclear. Constituent analysis has suggested that toxicity of this herb may be associated with tetrahydroxystilbene-O-(galloyl)-hex and emodin-O-hex-sulphate (an anthraquinone derivative).

One study comparing the toxicity of water extract and alcohol extract of PM indicated that alcohol extract had much stronger hepatotoxicity than water extract; the content of emodin-8-O-β-D-glucopyranoside, physcion-8-O-β-D-glucopyranoside, emodin, and physcion was significantly higher in alcohol extract than in water extract.

9.4 Severity and Clinical Course

Hepatotoxicity from Polygonum multiflorum is usually self-limited but can be prolonged and is occasionally fatal. Recurrence with restarting the herb is common and rechallenge should be avoided.

As administration time increases, the toxicity of PM gradually affects vitamin B6, bile acid, and bilirubin metabolism, leading to aggravated liver injury, abnormal biochemical indicators, and marked nephrotoxicity. The hepatotoxicity and nephrotoxicity caused by PM are both dynamic processes that affect different metabolic pathways at different administration times.

9.5 Raw vs. Processed Forms and Toxicity Differential

Both water and alcohol extracts of raw PM and processed ones have been studied, revealing distinct toxicological profiles. The primary toxicity of PM is hepatotoxicity, with mechanisms involving intrinsic and idiosyncratic factors. Traditional Chinese Medicine employs processing and compatibility techniques to reduce toxicity and enhance therapeutic effects.

These extracts can also lead to hepatotoxicity, nephrotoxicity, and embryonic toxicity.

9.6 Safety of Polygonum cuspidatum

Insufficient safety data exists for Japanese knotweed due to the lack of clinical data, but a human study of trans-resveratrol showed minimal toxicity with some gastrointestinal upset. The anthraquinone emodin, present in both P. cuspidatum and P. multiflorum, has documented potential for adverse effects at higher doses based on preclinical data. Multiple pharmacological studies have indicated that anthraquinones possess hepatotoxic potential. For example, in rats, emodin, rheinic acid, EG, physcion, and emodin-type monoanthone exhibit significant hepatotoxicity in liver microtissues.

9.7 Drug Interactions

There is scarce evidence in the body of literature demonstrating drug–drug interactions between Polygonum multiflorum and other herbs or medications. Based on the known pharmacology of its constituents, potential areas of concern include:

• CYP enzyme interactions: Water extract of PM treated groups showed significant inhibitions in CYP2E1 enzymatic activities and mRNA expressions.
• UGT enzyme inhibition: Stilbenes may impair UDP-glucuronosyltransferases (UGTs), potentially leading to drug-induced liver injury (DILI).
• HLA-associated polyphenol class effect: The HLA-B*35:01 allele is also linked to liver injury due to green tea (Camellia sinensis), Garcinia cambogia, and fo-ti (Polygonum multiflorum). These four herbs all have bioactive constituents that are polyphenols.

10. Regulatory and Pharmacopoeial Status

Polygonum multiflorum Thunb. (PMT), officially listed in the Chinese Pharmacopoeia, is one of the most popular perennial Chinese traditional medicines known as He shou wu in China and East Asia, and as Fo-ti in North America. Mounting pharmacological studies have stressed its key benefits for the treatment of various diseases and medical conditions such as liver injury, cancer, diabetes, alopecia, atherosclerosis, and neurodegenerative diseases.

The dried root of Polygonum cuspidatum Sieb. et Zucc. is one of the medicinal herbs listed in the Pharmacopoeia of the People's Republic of China. Both species are sold as dietary supplements in the United States, the European Union, and many other markets without requiring pre-market efficacy authorization.

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