Japanese Knotweed

In Chinese medicine the drug is Hu Zhang (虎杖), the dried rhizome and root of Reynoutria japonica, listed in the older literature as Polygonum cuspidatum ^{23Reference 23China Medical Information Platform (中国医药China Medical Information Platform (中国医药信息查询平台). 虎杖 Hu Zhang (Polygoni Cuspidati Rhizoma et Radix) — materia medica entry, reviewed under the National Administration of Traditional Chinese Medicine terminology project. https://www.dayi.org.cn/cmedical/301276View study →}. It is slightly bitter and slightly cold, and it enters the liver, gallbladder and lung channels ^{23Reference 23China Medical Information Platform (中国医药China Medical Information Platform (中国医药信息查询平台). 虎杖 Hu Zhang (Polygoni Cuspidati Rhizoma et Radix) — materia medica entry, reviewed under the National Administration of Traditional Chinese Medicine terminology project. https://www.dayi.org.cn/cmedical/301276View study →}.

Its functions follow from that profile: to drain dampness and clear jaundice, clear heat and resolve toxicity, disperse blood stasis and stop pain, and stop cough and transform phlegm ^{23Reference 23China Medical Information Platform (中国医药China Medical Information Platform (中国医药信息查询平台). 虎杖 Hu Zhang (Polygoni Cuspidati Rhizoma et Radix) — materia medica entry, reviewed under the National Administration of Traditional Chinese Medicine terminology project. https://www.dayi.org.cn/cmedical/301276View study →}.

It is used for damp-heat jaundice, cloudy or painful urination, vaginal discharge, and painful joints. It is also used for sores and boils, burns and scalds, and for blood-stasis patterns such as absent periods, abdominal masses and injuries from falls and blows, as well as cough from lung heat ^{23Reference 23China Medical Information Platform (中国医药China Medical Information Platform (中国医药信息查询平台). 虎杖 Hu Zhang (Polygoni Cuspidati Rhizoma et Radix) — materia medica entry, reviewed under the National Administration of Traditional Chinese Medicine terminology project. https://www.dayi.org.cn/cmedical/301276View study →}.

It is taken as a decoction of 9–15 g of the dried root and rhizome a day, and it is also soaked in wine or added to pills and powders ^{23,28Reference 23China Medical Information Platform (中国医药China Medical Information Platform (中国医药信息查询平台). 虎杖 Hu Zhang (Polygoni Cuspidati Rhizoma et Radix) — materia medica entry, reviewed under the National Administration of Traditional Chinese Medicine terminology project. https://www.dayi.org.cn/cmedical/301276View study →Reference 28Lin et al. · 2019In vitroInhibition of mitochondrial complex function — the hepatotoxicity mechanism of emodin based on quantitative proteomic analyses — in vitro study; states the Chinese Pharmacopoeia daily dose of 9–15 gView study →}. Externally it is applied as a powder, a strong decoction or an ointment for burns, sores and injuries ^{23Reference 23China Medical Information Platform (中国医药China Medical Information Platform (中国医药信息查询平台). 虎杖 Hu Zhang (Polygoni Cuspidati Rhizoma et Radix) — materia medica entry, reviewed under the National Administration of Traditional Chinese Medicine terminology project. https://www.dayi.org.cn/cmedical/301276View study →}. The Chinese Pharmacopoeia lists the dried rhizome and root as the official drug ^{23Reference 23China Medical Information Platform (中国医药China Medical Information Platform (中国医药信息查询平台). 虎杖 Hu Zhang (Polygoni Cuspidati Rhizoma et Radix) — materia medica entry, reviewed under the National Administration of Traditional Chinese Medicine terminology project. https://www.dayi.org.cn/cmedical/301276View study →}.

Western use of knotweed is recent. It entered Western herbal practice mainly through herbal protocols for Lyme disease, where the root extract is used as an antimicrobial and anti-inflammatory.

That reputation rests largely on a laboratory study in which Polygonum cuspidatum was one of the two most active of 12 botanicals tested against Borrelia burgdorferi ^{17Reference 17Feng et al. · 2020In vitroEvaluation of natural and botanical medicines for activity against growing and non-growing forms of Borrelia burgdorferi — in vitroView study →}. The rhizome is also valued as a source of stilbenes, above all resveratrol ^{29Reference 29Alperth et al. · 2021UHPLC analysis of Reynoutria japonica Houtt. rhizome preparations regarding stilbene and anthranoid composition and their antimycobacterial activity evaluation — analytical studyView study →}.

The mid-polarity fraction of an ethanol extract of the root most strongly reduced nitric oxide production in LPS-activated macrophages. It contained 31 identified compounds: 12 anthraquinones, 7 stilbenes, 9 phenols and 3 others ^{2Reference 2Yu et al. · 2021In vitroAnti-inflammatory constituents in the root and rhizome of Polygonum cuspidatum by UPLC-PDA-QTOF/MS and LPS-activated RAW264.7 macrophages — in vitroView study →}. Of the five major constituents measured, resveratrol and two emodin glucosides lowered NO, TNF-α, IL-6 and MCP-1 ^{2Reference 2Yu et al. · 2021In vitroAnti-inflammatory constituents in the root and rhizome of Polygonum cuspidatum by UPLC-PDA-QTOF/MS and LPS-activated RAW264.7 macrophages — in vitroView study →}.

In mice with acute lung injury, a root extract reduced lung damage and inflammation, and its luteolin protected macrophages from cell death through AKT1 ^{3Reference 3Huang et al. · 2026In vitroReynoutria japonica and its component luteolin treat acute lung injury by targeting AKT1 — in vivo mouse and in vitro studyView study →}. In rats with complete Freund’s adjuvant arthritis, the root reduced paw swelling and arthritis scores and suppressed NF-κB signalling ^{4Reference 4Li et al. · 2025AnimalActivation of the NF-κB pathway by Reynoutria japonica Houtt ameliorates complete Freund’s adjuvant arthritis — rat modelView study →}. In a rat model of osteoarthritis it reduced pain and cartilage breakdown ^{5Reference 5Jo et al. · 2024AnimalInhibitory effects of Reynoutria japonica Houtt on pain and cartilage breakdown in osteoarthritis — animal modelView study →}.

The effects are consistent, but active doses and fractions vary between studies.

Gap: No human trial has tested the root alone for any inflammatory condition.

An extract made with a natural deep eutectic solvent, yielding about 3 mg of resveratrol per gram of root, scavenged ABTS, DPPH and hydroxyl radicals in vitro ^{6Reference 6Guo et al. · 2026In vitroOptimisation of extraction and antioxidant activities of resveratrol from Polygonum cuspidatum — in vitroView study →}.

Polydatin activates the Nrf2 antioxidant pathway and suppresses ferroptosis in the blood vessels of mice ^{8Reference 8Wu et al. · 2025AnimalNrf2-mediated inhibition of ferroptosis contributes to amelioration of atherosclerosis by polydatin — ApoE-knockout mouse, in vivoView study →}.

Gap: Almost entirely in vitro and constituent-level; whole-root antioxidant benefit has not been demonstrated in humans, and free-resveratrol data overstate what a polydatin-dominant root delivers.

A systematic review pooled eight randomised trials (1,123 participants) of knotweed, under the name Fallopia japonica, for acute respiratory infections. In seven trials (1,013 participants), herbal mixtures containing it raised the rate of symptom improvement (risk ratio 1.14, 95% CI 1.09–1.20, I² = 0%). They also shortened fever and lowered Murray lung-injury scores, without more adverse events ^{1Reference 1Wang et al. · 2022Meta-analysisReynoutria japonica Houtt for acute respiratory tract infections in adults and children — a systematic review and meta-analysis of randomised controlled trialsView study →}.

⚠ In every trial knotweed was one part of a multi-herb mixture, and in all but one the mixture was given alongside antibiotics ^{1Reference 1Wang et al. · 2022Meta-analysisReynoutria japonica Houtt for acute respiratory tract infections in adults and children — a systematic review and meta-analysis of randomised controlled trialsView study →}.

Gap: No RCT has tested knotweed as a single herb for respiratory infection; the pooled benefit belongs to the formulas, not necessarily to R. japonica.

A whole knotweed extract lowered blood lipids in rats with high blood fats, acting through the PI3K/AKT/FOXO3 pathway. Twelve main active ingredients were identified, with polydatin and resveratrol as the leading ones ^{7Reference 7Tao et al. · 2021AnimalPolygonum cuspidatum extract exerts antihyperlipidemic effects by regulation of the PI3K/AKT/FOXO3 pathway — in vivo rat modelView study →}.

Isolated polydatin reduced plaque in ApoE-knockout mice by blocking ferroptosis through Nrf2 ^{8Reference 8Wu et al. · 2025AnimalNrf2-mediated inhibition of ferroptosis contributes to amelioration of atherosclerosis by polydatin — ApoE-knockout mouse, in vivoView study →}. In rat aorta exposed to high glucose, it restored the relaxation of blood vessels and lowered NLRP3 and VCAM-1 ^{10Reference 10Shah et al. · 2025AnimalPolydatin enhances blood-vessel relaxation and reduces NLRP3-mediated inflammation in hyperglycaemia — rat aorta, ex vivoView study →}. A ginseng–knotweed herb pair also reduced plaque in ApoE-knockout mice, with changes in gut bacteria ^{9Reference 9Wang et al. · 2026AnimalPanax ginseng–Polygonum cuspidatum alleviates atherosclerosis in ApoE(-/-) mice — in vivo animal modelView study →}.

Most of this work uses purified polydatin, not the whole root.

Gap: There are no human cardiovascular data for the root.

A review of cholestatic liver injury found that polydatin, resveratrol, emodin and quercetin protect the liver in animal models, by regulating bile acids through FXR, PXR and the bile salt export pump ^{11Reference 11Zhang et al. · 2025ReviewProtective effects of Polygonum cuspidatum bioactive constituents against cholestatic liver injury — a mechanistic reviewView study →}. A whole extract protected liver mitochondria in rats with fatty liver disease ^{12Reference 12Yu et al. · 2022AnimalIn vivo identification of the pharmacodynamic ingredients of Polygonum cuspidatum for remedying mitochondria in MAFLD — rat modelView study →}.

⚠ A meta-analysis of 28 rodent studies (537 animals) found that emodin is both protective and toxic to the liver. At controlled doses and durations it lowered liver-injury markers, mainly by suppressing CYP2E1 expression and activating the FXR/BSEP pathway. Higher doses and longer use raised liver injury markers, and the model put the tipping point in rodents at about 46 mg/kg a day or 30 days ^{14Reference 14Hu et al. · 2025Meta-analysisThe efficacy and toxicity equilibrium of emodin for liver injury — a bidirectional meta-analysis and machine-learning study of rodent modelsView study →}.

In a 72-year-old patient, liver injury followed 14 days of a Hu Zhang–containing formula. It was scored as probable on the RUCAM scale, and liver function returned to normal after N-acetylcysteine and supportive treatment ^{15Reference 15Liang et al. · 2026Case reportA case report and literature review of drug-induced liver injury caused by Huzhang according to the updated RUCAMView study →}.

Gap: Protection and harm both trace to the same anthraquinone chemistry; the dose and duration that invert the effect in humans are unknown.

A 2026 study found that people with high uric acid had raised blood levels of leucine, phenylalanine and tyrosine. In rats with high uric acid, P. cuspidatum reversed these changes, reduced kidney damage and altered gut bacteria ^{16Reference 16Ma et al. · 2026AnimalPolygonum cuspidatum alleviates hyperuricaemia-induced renal injury via rectifying amino-acid metabolism — human serum metabolomics with rat validationView study →}.

A registered Phase 2 trial, NCT04462666, planned to compare Huzhang granules with etoricoxib in 267 people with acute gouty arthritis.

Gap: The treatment data are from rats; the registered gout trial has carried “unknown” status since 2020 with no results posted.

Knotweed’s place in Lyme disease protocols rests on a laboratory study. Of 12 botanical extracts tested against Borrelia burgdorferi, Polygonum cuspidatum was one of the two most active. It inhibited growing bacteria (MIC 0.25–0.5%) and was also active against dormant, antibiotic-tolerant forms ^{17Reference 17Feng et al. · 2020In vitroEvaluation of natural and botanical medicines for activity against growing and non-growing forms of Borrelia burgdorferi — in vitroView study →}.

In the same study, only Cryptolepis sanguinolenta (cryptolepis) wiped out the dormant forms on subculture. Knotweed did not ^{17Reference 17Feng et al. · 2020In vitroEvaluation of natural and botanical medicines for activity against growing and non-growing forms of Borrelia burgdorferi — in vitroView study →}.

Gap: The anti-Borrelia data are entirely in vitro, at extract concentrations that may not be reached in tissue; there is no animal or human evidence that oral knotweed treats Lyme disease.

Anticancer research centres on isolated polydatin. A review compiles its reported effects on cancer cell growth, migration, spread and death across several cancer types ^{18Reference 18Imtiyaz et al. · 2025ReviewPolydatin — a natural compound with multifaceted anticancer properties — reviewView study →}.

A knotweed extract converted by microbes to raise its resveratrol content slowed the growth of lung cancer cells in the laboratory and in mice. It worked better than the unconverted extract, and a 28-day rat study found no treatment-related harm ^{22Reference 22Wang et al. · 2026In vitroResveratrol-enriched Polygonum cuspidatum extract enhances functional bioactivity against non-small cell lung cancer through modulation of inflammatory signaling and mitochondrial apoptosis — in vitro, mouse xenograft and 28-day rat safety studyView study →}.

Gap: There are no human cancer data.

An acidic pectic polysaccharide of about 134 kDa, isolated from the root, relieved DSS-induced colitis in mice. It reduced colonic inflammation, helped restore the gut barrier and raised Alistipes and Akkermansia in the gut microbiota ^{20Reference 20Fu et al. · 2026AnimalPectic polysaccharides from Polygonum cuspidatum — structural characterisation and protective effects against DSS-induced colitis — mouse modelView study →}.

An aqueous root extract eased a damp-heat model of ulcerative colitis in mice. It lowered inflammatory factors, reduced mucosal damage, shifted the gut bacteria and raised short-chain fatty acids ^{21Reference 21Jiang et al. · 2025AnimalThe aqueous extract of Reynoutria japonica ameliorates damp-heat ulcerative colitis in mice by modulating gut microbiota — in vivoView study →}.

Gap: Both results are from mouse models, with whole-root preparations rather than isolated stilbenes; there are no human data.

Side effects. The most predictable effect at traditional doses is a laxative one, from the root’s anthraquinone emodin.

Liver. A meta-analysis of 28 rodent studies found that emodin protects the liver at controlled doses and durations and raises liver injury markers as either increases ^{14Reference 14Hu et al. · 2025Meta-analysisThe efficacy and toxicity equilibrium of emodin for liver injury — a bidirectional meta-analysis and machine-learning study of rodent modelsView study →}. In a 72-year-old patient, probable drug-induced liver injury followed 14 days of a Hu Zhang–containing formula and resolved with N-acetylcysteine and supportive treatment ^{15Reference 15Liang et al. · 2026Case reportA case report and literature review of drug-induced liver injury caused by Huzhang according to the updated RUCAMView study →}.

The authors advised caution in elderly patients, long-term users and people with a history of surgery ^{15Reference 15Liang et al. · 2026Case reportA case report and literature review of drug-induced liver injury caused by Huzhang according to the updated RUCAMView study →}. Avoid it with existing liver disease.

Overdose. No human overdose data are published. The dose-dependent liver signal comes from rodent models and a single case report ^{14,15Reference 14Hu et al. · 2025Meta-analysisThe efficacy and toxicity equilibrium of emodin for liver injury — a bidirectional meta-analysis and machine-learning study of rodent modelsView study →Reference 15Liang et al. · 2026Case reportA case report and literature review of drug-induced liver injury caused by Huzhang according to the updated RUCAMView study →}.

Liver-toxic drugs. An added strain on the liver with other hepatotoxic medicines is plausible but has not been tested.

Anticoagulant and antiplatelet drugs. Chinese medicine classes Hu Zhang as a herb that moves the blood ^{23Reference 23China Medical Information Platform (中国医药China Medical Information Platform (中国医药信息查询平台). 虎杖 Hu Zhang (Polygoni Cuspidati Rhizoma et Radix) — materia medica entry, reviewed under the National Administration of Traditional Chinese Medicine terminology project. https://www.dayi.org.cn/cmedical/301276View study →}, so an added effect with anticoagulant or antiplatelet drugs is plausible. It has not been studied in people.

Laxatives and potassium-lowering drugs. As a stimulant laxative, the root could add to the effect of other laxatives and to potassium loss with diuretics or corticosteroids if taken for long periods. This has not been studied.

Drug metabolism. There is no human drug-interaction study of the whole root and no confirmed CYP450 effect. In the laboratory, emodin inhibited CYP1A1, CYP1A2 and CYP2B1 ^{31Reference 31Sridhar J et al. · 2012In vitroInhibition of cytochrome p450 enzymes by quinones and anthraquinones — in vitroView study →}. In 42 healthy volunteers, purified resveratrol at 1 g a day for four weeks inhibited CYP3A4, CYP2D6 and CYP2C9 activity and induced CYP1A2 ^{30Reference 30Chow HH et al. · 2010Clinical trialResveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study — clinical trialView study →}.

The root holds resveratrol at low levels, mostly as its glucoside polydatin ^{22Reference 22Wang et al. · 2026In vitroResveratrol-enriched Polygonum cuspidatum extract enhances functional bioactivity against non-small cell lung cancer through modulation of inflammatory signaling and mitochondrial apoptosis — in vitro, mouse xenograft and 28-day rat safety studyView study →}, so neither finding has been confirmed for a decoction. In rats, giving knotweed together with cinnamon twig (Guizhi) changed the blood and tissue levels of polydatin, resveratrol and emodin ^{19Reference 19Yang et al. · 2024AnimalComparative pharmacokinetics and tissue distribution of polydatin, resveratrol and emodin after oral Huzhang and Huzhang-Guizhi extracts — in vivo rat studyView study →}.

Children. Not specifically studied. The anthraquinone laxative content argues against routine use in children.

Wild-collected root. Knotweed growing on polluted riverbank soils takes up metals such as lead and zinc ^{24Reference 24Miletić et al. · 2024Phytoremediation potential of invasive plant species for potentially toxic elements along the Sava River upstream — field studyView study →}. In the UK it commonly grows on roadsides, waste ground, railway embankments and spoil tips ^{27Reference 27GOV.UK (Environment Agency)Japanese knotweed: prevent it from spreading — government guidanceView study →}.

Preparation. What a preparation carries depends on how it is made. In one analysis of the rhizome, the decoction held the most anthranoids, while a 38% ethanol macerate held the most stilbenes and few anthranoids ^{29Reference 29Alperth et al. · 2021UHPLC analysis of Reynoutria japonica Houtt. rhizome preparations regarding stilbene and anthranoid composition and their antimycobacterial activity evaluation — analytical studyView study →}. Extracts standardised to resveratrol can deliver far more stilbene than a traditional decoction, and the traditional safety record comes from the decoction.