Stilbene Glycosides

Compound Class	Stilbene glycosides — glucosylated stilbenes; structurally related to resveratrol
Representative Members	2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) — the dominant and marker compound
Botanical Sources	Polygonum multiflorum (fo-ti; he shou wu; Chinese knotweed)
Plant Part(s)	Tuberous root
Typical Standardisation	Stilbene glycosides (as TSG) by HPLC; 5% common commercial grade
Primary Applications	Traditional tonic and hair-pigmentation positioning; antioxidant research
Claim Strength (Overview)	Emerging — and this compound carries a well-documented hepatotoxicity signal that must be surfaced before any efficacy discussion
Buy from Herbuno	Stilbene Glycosides 5% Powder (Fo-Ti Extract) | Standardized Polygonum multiflorum → Resveratrol 50% Powder (Japanese Knotweed Extract) | Standardized Polygonum cuspidatum →

Name origin: Stilbene glycoside denotes the structural class — a stilbene backbone (two aromatic rings joined by an ethene bridge, the same skeleton as resveratrol) bearing a glucose unit. The dominant member, 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside, is universally abbreviated TSG. The source plant’s Chinese name, he shou wu, translates roughly as "Mr He’s black hair," from a legend of an elderly man restoring youthful dark hair by consuming the root. Traditional use: Polygonum multiflorum has been used in Traditional Chinese Medicine since at least the Song Dynasty, traditionally to nourish the liver and kidneys, supplement essence and blood, strengthen bones and tendons, and address dizziness, tinnitus, and premature greying — the hair-blackening reputation being the most commercially exploited. There is a bitter irony in the traditional liver-tonifying indication, given what modern pharmacovigilance has established about this herb. Safety context: This monograph departs from the usual structure because the dominant fact about this compound class is not its efficacy but its safety signal. Polygonum multiflorum is one of the most extensively documented causes of herb-induced liver injury worldwide, with a dedicated LiverTox entry, a substantial case-report literature spanning multiple countries, an identified genetic risk allele, and reports of prolonged and occasionally fatal outcomes. Anything written about this ingredient that leads with tonic benefits and buries the liver risk would be dishonest, and this page does not do that. Commercial source: Polygonum multiflorum root extract standardized to stilbene glycoside (TSG) content is the commercial format. Note that Polygonum cuspidatum — the resveratrol source — is a different species with a different safety profile.

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Evidence for Stilbene Glycosides Applications

The hepatotoxicity of Polygonum multiflorum is authoritatively documented and must be stated first. According to LiverTox, the mechanism of injury is usually attributed to the anthraquinones such as emodin, though in one report the major compound identified in recovered tablets was a stilbene glycoside — tetrahydroxystilbene-glucopyranoside. Critically, the HLA allele B*35:01 appears to be a major risk factor for liver injury from Polygonum multiflorum, suggesting the injury is immunologically mediated; hepatotoxicity is usually self-limited but can be prolonged and is occasionally fatal, recurrence on restarting the herb is common, and rechallenge should be avoided (LiverTox NIDDK). "Occasionally fatal" is the operative phrase, and it belongs in the first paragraph of any honest account of this ingredient. Claim strength: High (established adverse signal).

The relationship between the marketed compound and the toxicity is genuinely uncomfortable rather than conveniently separable. A review of the potential hepatotoxic components of Polygonum multiflorum notes that stilbenes, especially TSG, are considered to be the main liver-protective components of the plant — and yet research has found that TSG might itself be associated with the hepatotoxicity, with the ingestion of a wide range of PM formulations at a wide range of doses reported to cause liver injury (Front Pharmacol 2020). In other words, the compound this extract is standardized on is itself implicated in the injury. That is not a footnote — it is the central fact a formulator needs. Claim strength: Emerging (mechanism unresolved).

The injury pattern appears idiosyncratic rather than dose-predictable, which is precisely what makes it difficult to manage through dosing discipline. Liver injury has been reported across a wide range of doses and durations — from days to months — and across many preparation types including steamed and wine-processed root, powders, oral liquids, capsules, and teas. Idiosyncratic drug-induced liver injury is, by definition, not reliably avoidable by staying under a threshold, and formulators should not assume a low serving size confers safety. Claim strength: Moderate.

Genetic and metabolic susceptibility factors are emerging with some clarity. Beyond the HLA-B*35:01 association noted above, clinical work has found that CYP1A2 genetic polymorphism differs between the normal population and patients with PM-induced liver injury, with lower CYP1A2 enzyme activity in affected patients, and experimental work has shown that inhibiting drug-metabolizing enzymes increases liver injury induced by stilbene glycoside. This points to a susceptible subpopulation rather than uniform toxicity — but since that subpopulation cannot be identified prospectively without genotyping, it offers little practical reassurance. Claim strength: Emerging.

A processing and stability finding with direct formulation relevance: cis-stilbene glycoside has been found to have the strongest cytotoxicity of the forms examined, leading researchers to recommend that Polygonum multiflorum be stored in the dark during preservation of alcohol-derived or liquid preparations to avoid or reduce formation of the cis isomer. This is an actionable handling specification. It has also been noted that current pharmacopoeial quality standards for PM specify only minimum limits for stilbene glycoside and anthraquinone content and are silent on upper limits — a genuine regulatory gap given that these are the constituents implicated in toxicity. Claim strength: Moderate.

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Dosage & Formulator Specification

Herbuno carries Polygonum multiflorum root extract standardized to 5% stilbene glycosides. Buyers must not confuse this with Polygonum cuspidatum (Japanese knotweed), a different species that is the standard commercial source of resveratrol and carries a different safety profile — Herbuno also stocks resveratrol at 98%, 50%, and 20% from P. cuspidatum. Confusing the two species is a real and consequential sourcing trap given the hepatotoxicity signal attached to P. multiflorum specifically.

this material for formulators who have made an informed decision about the risk profile is available from Herbuno, and it would be irresponsible to present a confident dosing recommendation for an ingredient whose principal documented pharmacology is idiosyncratic liver injury. There is no established safe-dose threshold: injury has been reported across a wide dose range and across preparation types, and its idiosyncratic character means low serving size does not reliably confer safety. Any formulator using this ingredient should treat conservative dosing as risk-reduction, not risk-elimination.

Analytical verification should specify stilbene glycoside content as TSG by HPLC, with free and combined anthraquinone content (particularly emodin) quantified separately, since anthraquinones are the constituents most commonly implicated in the hepatotoxicity mechanism. Given the cytotoxicity finding for the cis isomer, the trans:cis stilbene glycoside ratio should be characterized, and light-protected storage should be specified for liquid and alcohol-derived preparations. Note the pharmacopoeial gap: current standards give minimum limits only and are silent on upper limits for the toxicity-implicated constituents.

Any product containing Polygonum multiflorum should carry clear and prominent liver-injury warning language. The documented picture is: idiosyncratic herb-induced liver injury, presenting as acute hepatitis and occasionally as acute liver failure; usually self-limited on discontinuation but sometimes prolonged and occasionally fatal; common recurrence on rechallenge, which should be avoided; and an identified immunological risk allele (HLA-B*35:01). Consumers should be advised to discontinue immediately and seek medical attention on any sign of jaundice, dark urine, abdominal pain, or unexplained fatigue. Concurrent use with other hepatotoxic agents or alcohol warrants specific caution. Formulators in regulated markets should confirm the current status of this ingredient with their regulator, as several jurisdictions have imposed restrictions.

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Frequently Asked Questions — Stilbene Glycosides

Is Polygonum multiflorum safe?
It carries a well-documented hepatotoxicity signal and should not be treated as routinely safe. LiverTox records that injury is usually self-limited but can be prolonged and is occasionally fatal, with common recurrence on restarting the herb. The HLA-B*35:01 allele is a major risk factor, suggesting immune-mediated injury. Any product containing it needs prominent liver-injury warning language.

Is the stilbene glycoside itself the toxic component?
This is genuinely unresolved and uncomfortable. Anthraquinones such as emodin are most commonly implicated, but one report identified the stilbene glycoside as the major compound in recovered tablets, and research suggests TSG may be associated with the hepatotoxicity — despite stilbenes also being considered the plant's main liver-protective constituents. The compound the extract is standardized on is itself implicated.

Is fo-ti the same as Japanese knotweed?
No, and confusing them is a consequential error. Fo-ti / he shou wu is Polygonum multiflorum, the hepatotoxicity-associated species. Japanese knotweed is Polygonum cuspidatum, the standard commercial resveratrol source, with a different safety profile. They are different species and must not be substituted.

Can a low dose avoid the liver risk?
Not reliably. The injury pattern appears idiosyncratic rather than dose-predictable — liver injury has been reported across a wide range of doses and durations, from days to months, and across many preparation types. Idiosyncratic injury is by definition not avoidable by staying under a threshold, so conservative dosing is risk-reduction, not risk-elimination.

Related compounds: Resveratrol, Pterostilbene, Polyphenols, Baicalein

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Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.

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