Ba Jiao Lian

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Dysosma versipellis (Hance) M.Cheng ex Ying

Not yet clinically reviewed

Pinyin: Ba Jiao Lian
Sixangular Dysosma Rhizome

Traditionally used for

  • Cough & breathing
  • Digestion
  • Bowel health
  • Skin

Cautions & contraindications

  • Pregnancy
  • Toxic — professional use only
Moderate evidence · 6 studies

☯ TCM Properties

Category: clearing heat
Temperature: neutral
Taste: bitter, pungent
Meridians: lung, liver
Functions:

Removes toxic Heat, resolves Phlegm, disperses nodulation, removes Stagnation and reduces swelling

Traditional Chinese Uses

Ba Jiao Lian is the rhizome of Dysosma versipellis, a Chinese relative of mayapple, bitter and pungent, cool and toxic, entering the Lung and Liver channels. It clears toxic Heat, resolves Phlegm, disperses nodulation, dispels Stagnation and reduces swelling. It has been used for toxic swellings, sores and abscesses, scrofula and nodules, mumps, snakebite, and cough with Phlegm, generally applied in small doses or topically as a paste.

The rhizome is significantly toxic owing to podophyllotoxin. Overdose produces a serious syndrome of nausea, vomiting and diarrhea followed by confusion, coma, liver and blood abnormalities, and sensory-motor neuropathy; fatalities are reported. It must be used only in strictly controlled doses by qualified practitioners and is contraindicated in pregnancy.

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Botanical Description

Dysosma versipellis is a rhizomatous perennial herb of the Berberidaceae, closely allied to the North American mayapple (Podophyllum peltatum). It grows to about 20–40 cm from a stout, knotty horizontal rhizome bearing fibrous roots. Each stem typically bears one or two large peltate, palmately lobed leaves with 6–9 angular lobes, the lamina deep green and often mottled when young. Pendulous, dark red to maroon flowers cluster beneath the leaves in late spring, followed by a fleshy reddish berry. The plant occurs in moist, shaded forests and ravines of central and southern China. The rhizome accumulates podophyllotoxin and related lignans, rendering the plant highly toxic; medicinal use requires strict processing and professional supervision.

Active Constituents

Podophyllotoxin

Aryltetralin lignan

Concentration: 37.21 mg/g of the dried roots by quantitative HPLC, i.e. roughly 3.7 percent - comparable to Podophyllum hexandrum, the commercial source of the lignan

The principal toxic constituent of the drug. It binds the colchicine site of tubulin and arrests cells in G2/M; in vitro it inhibited androgen-sensitive (LNCaP) and androgen-independent (PC-3) prostate cancer cells with IC50 values of about 0.030-0.056 microM. In whole animals and in people the same antimitotic action produces gastrointestinal, hepatic, renal, haematological and neurological injury. It is the parent compound from which etoposide and teniposide are semisynthesised, and it is the reason a decoction or medicinal wine of this rhizome can kill.

Deoxypodophyllotoxin

Aryltetralin lignan

Concentration: 5.01 mg/g of the dried roots by quantitative HPLC

The second most abundant lignan in the root. It is comparably cytotoxic to podophyllotoxin against prostate cancer lines in vitro and adds to the total antimitotic burden of the crude drug.

4'-Demethylpodophyllotoxin

Aryltetralin lignan

Concentration: 2.75 mg/g of the dried roots by quantitative HPLC

A demethylated congener of podophyllotoxin with similar sub-micromolar cytotoxicity in cell culture. It is also one of the constituents flagged as hepatotoxic in multi-omics toxicology work on the herb.

Podophyllotoxin-4-O-D-glucoside

Lignan glycoside

Identified as one of five potential hepatotoxic components of Dysosma versipellis in a toxicological-evidence-chain study, alongside podorhizol, podophyllotoxin, podophyllotoxone and 3',4'-O,O-didemethylpodophyllotoxin. Glycosidic lignans are a reservoir that can be hydrolysed to the free aglycone.

Diphyllin

Arylnaphthalene lignan

A minor lignan of the root, less cytotoxic in the prostate cancer assay than the aryltetralin series but of interest as a vacuolar ATPase inhibitor in other work.

Dysosmarol

Monoepoxylignan

A lignan first described from the roots of this species. It was substantially less active than podophyllotoxin, deoxypodophyllotoxin and 4'-demethylpodophyllotoxin against prostate cancer cell lines.

Quercetin

Flavonol

A co-occurring flavonol of the root. In Vero cells and in Swiss mice, quercetin given with podophyllotoxin reduced cytotoxicity, mortality and liver and kidney damage, apparently by competing for the same colchicine binding site on tubulin and by antioxidant action. This does not make the crude herb safe; it is a finding about a possible antidote.

Kaempferol

Flavonol

The second co-occurring flavonol shown to protect against podophyllotoxin toxicity in the same mouse model, reducing 7-day mortality from 80 percent (podophyllotoxin alone, 40 mg/kg) to 30 percent.

beta-Sitosterol

Phytosterol

A ubiquitous plant sterol isolated from the roots; not implicated in the toxicity of the drug.

⚠ Drug Interactions

Etoposide, teniposide and other cytotoxic chemotherapy

Major Evidence: Probable

Etoposide and teniposide are semisynthetic derivatives of podophyllotoxin, the constituent that makes up roughly 3.7 percent of this root. Case series of Bajiaolian poisoning document thrombocytopenia, leucopenia and abnormal liver function tests from the herb alone. Giving the crude herb alongside a cytotoxic regimen stacks the same mechanism of injury, and no dose of the crude drug is standardised.

Clinical note: Do not use Ba Jiao Lian in any patient receiving chemotherapy. If a patient on chemotherapy reports taking it, stop it and check a full blood count and liver function.

Topical podophyllin or podophyllotoxin preparations for anogenital warts

Major Evidence: Probable

Topical podophyllotoxin is absorbed, and systemic podophyllin poisoning from topical use is a long-recognised cause of severe peripheral neuropathy and bone-marrow suppression. Oral Ba Jiao Lian delivers the identical toxin, so the two exposures are additive and there is no separate margin of safety.

Clinical note: Treat concurrent use as an overdose situation. The therapeutic and toxic doses of this herb are close enough that any added podophyllotoxin exposure is unacceptable.

Myelosuppressive drugs (methotrexate, azathioprine, chloramphenicol, linezolid)

Major Evidence: Possible

Transient bone-marrow and hepatic toxicity is documented in human Bajiaolian intoxication. Adding a drug that independently suppresses the marrow removes the reserve the patient would otherwise recover on.

Clinical note: Avoid the combination. Bajiaolian intoxication has been misdiagnosed as acute gastroenteritis in 15 of 17 Taiwanese poison-centre cases, so cytopenias in a patient with recent gastrointestinal upset should prompt a direct question about herbal use.

Hepatotoxic drugs (paracetamol/acetaminophen, isoniazid, methotrexate, azole antifungals)

Major Evidence: Possible

Multi-omics toxicology work identified five hepatotoxic lignans in Dysosma versipellis (podophyllotoxin-4-O-D-glucoside, podorhizol, podophyllotoxin, podophyllotoxone and 3',4'-O,O-didemethylpodophyllotoxin) acting through oxidative stress, apoptosis and inflammatory signalling, and abnormal liver function tests are reported in human poisoning cases.

Clinical note: Do not combine. Any patient who has taken this herb needs liver function tests regardless of concurrent medication.

Dysosma pleiantha and Podophyllum hexandrum sold under the same names Ba Jiao Lian and Gui Jiu

Major Evidence: Established

Ba Jiao Lian and the older name Gui Jiu are applied in the market to several Dysosma species and to Podophyllum hexandrum. Dysosma pleiantha is the species behind most of the Taiwanese poisoning literature, where Bajiaolian is the fifth most common cause of herbal poisoning; Dysosma versipellis roots contain podophyllotoxin at a similar concentration to Podophyllum hexandrum, the commercial source used for etoposide manufacture. A practitioner has no way to tell from the dried rhizome which species, or what lignan content, is in the packet.

Clinical note: Treat all Ba Jiao Lian and Gui Jiu material as interchangeable in hazard. This herb is not in the Chinese Pharmacopoeia, has no standardised assay, and should not be dispensed for internal use.

Dosage

Form Amount Frequency Duration Population Notes
decoction Dose not established here — see note — — — No Chinese Pharmacopoeia 2025 monograph found for this drug, so no pharmacopoeial dose is given here. *Dysosma versipellis* contains podophyllotoxin, an antimitotic that is severely toxic by ingestion — poisoning causes vomiting, hepatic and renal injury, bone-marrow suppression and a delayed, sometimes irreversible peripheral neuropathy, and fatalities are documented from herbal use. Contraindicated in pregnancy. Mainly applied externally. The previous value was generic filler generated from tcm_category and was cleared; it has not been replaced with an estimate.

Evidence Tier

Moderate evidence · 6 studies

Recorded studies by study design, strongest design at the top. This is a study-design tier only, not a GRADE rating: it does not weigh risk of bias, consistency or precision.

Verified: design read from PubMed for a DOI that resolves to the cited paper Unverified: taken from the study's recorded description

Clinical Studies

Podophyllotoxin Intoxication: Toxic Effect of Bajiaolian in Herbal Therapeutics

Kao WF, Hung DZ, Tsai WJ, Lin KP, Deng JF (1992) Human & Experimental Toxicology case series Verified: Observational / case report

Five people who drank infusions made with Bajiaolian developed nausea, vomiting, diarrhoea and abdominal pain, followed by thrombocytopenia, leucopenia, abnormal liver function tests, sensory ataxia, altered consciousness and persistent peripheral tingling or numbness. The report established the multi-stage clinical picture of podophyllotoxin poisoning from this herb.

Bajiaolian poisoning—a poisoning with high misdiagnostic rate

Chou SL, Chou MY, Kao WF, Yen DH, Yen LY, Huang CI, Lee CH (2010) The American Journal of Emergency Medicine case series

Records of four major Taiwanese poison centres from July 1985 to March 2003 identified 17 patients with Bajiaolian intoxication, of whom 15 (88.2 percent) were misdiagnosed at first contact; 14 were labelled acute gastroenteritis. The authors attribute this to the biphasic course, in which gastrointestinal symptoms precede the neurological ones, and note that in Taiwan Bajiaolian is the fifth commonest cause of herbal poisoning.

Sensory Neuropathy due to Bajiaolian (Podophyllotoxin) Intoxication

Chu CC, Huang CC, Chu NS (2000) European Neurology case report Verified: Observational / case report

A Taiwanese neurology report of sensory neuropathy following Bajiaolian (podophyllotoxin) intoxication. No abstract is indexed with the record, so only the outcome named in the title can be verified from the citation; it is cited here as part of the documented pattern of peripheral nerve injury after ingestion of this rhizome.

Alleviation of Podophyllotoxin Toxicity Using Coexisting Flavonoids from Dysosma versipellis

Li J, Sun H, Jin L, Cao W, Zhang J, Guo CY, Ding K, Luo C, Ye WC, Jiang RW (2013) PLoS ONE animal Verified: In vitro / animal

In Vero cells, quercetin and kaempferol reversed podophyllotoxin-induced G2/M arrest, reactive oxygen species generation, membrane-potential change and microtubule disruption. In Swiss mice given podophyllotoxin 40 mg/kg for three days, mortality at day 7 was 80 percent with podophyllotoxin alone, 20 percent with added quercetin (150 mg/kg) and 30 percent with added kaempferol; transaminases, alkaline phosphatase, lactate dehydrogenase, urea, creatinine and malondialdehyde all fell and superoxide dismutase and glutathione rose. Tubulin assembly and docking work indicated the flavonoids compete for the colchicine binding site. This is a search for an antidote, not evidence that the crude herb is safe.

Study on potential toxic material base and mechanisms of hepatotoxicity induced by Dysosma versipellis based on toxicological evidence chain (TEC) concept

Liu C, Zhang C, He T, Sun L, Wang Q, Han S, Wang W, Kong J, Yuan F, Huang J (2020) Ecotoxicology and Environmental Safety animal Verified: In vitro / animal

Combining chemomics, metabolomics, molecular docking and network toxicology, the authors identified five candidate hepatotoxic constituents of Dysosma versipellis: podophyllotoxin-4-O-D-glucoside, podorhizol, podophyllotoxin, podophyllotoxone and 3',4'-O,O-didemethylpodophyllotoxin. These affected phenylalanine, glycerophospholipid and energy metabolism through PAH, SOD1 and SOD2, inducing oxidative stress, apoptosis and inflammation leading to liver injury.

Lignans from Dysosma versipellis with Inhibitory Effects on Prostate Cancer Cell Lines

Jiang RW, Zhou JR, Hon PM, Li SL, Zhou Y, Li LL, Ye WC, Xu HX, Shaw PC, But PP (2007) Journal of Natural Products in vitro

Nine compounds were isolated from the roots, including the new monoepoxylignan dysosmarol plus podophyllotoxin, 4'-demethylpodophyllotoxin, deoxypodophyllotoxin, 4'-demethyldeoxypodophyllotoxin, diphyllin, kaempferol, quercetin and beta-sitosterol. The aryltetralin lignans inhibited LNCaP and PC-3 prostate cancer cells with IC50 values of 0.030-0.056 and 0.032-0.082 microM. Quantitative HPLC put podophyllotoxin at 37.21 mg/g, deoxypodophyllotoxin at 5.01 mg/g and 4'-demethylpodophyllotoxin at 2.75 mg/g, a podophyllotoxin content similar to that of Podophyllum hexandrum.

Historical Texts

Shen Nong Ben Cao Jing

Han dynasty
The drug gui jiu is listed among the lower-grade (xia pin) medicines, the class explicitly reserved for toxic drugs used briefly to attack disease rather than for long-term supplementation. Later Chinese materia medica identify gui jiu with Dysosma rhizomes, though the historical name has also covered Podophyllum hexandrum and several Dysosma species, so the classical identification is retrospective rather than secure.

Ben Cao Gang Mu

Ming dynasty (Li Shizhen, 1596)
Gui jiu is carried forward as a toxic drug used to break up masses and nodules, disperse swelling and treat snakebite - the same indications for which Ba Jiao Lian is used in modern folk practice for lymphadenopathy, neck masses and snakebite. The classical texts do not describe the delayed neuropathy and marrow suppression that modern poison-centre series document.

Conservation status

Modern (IUCN Red List; China National Key Protected Wild Plants list, 2021)
Dysosma versipellis is endemic to China, assessed as Vulnerable (A2cd) on the IUCN Red List, and listed as a Class II nationally protected wild plant in China. Wild populations have been driven towards exhaustion by habitat loss and by digging for the trade, partly because the rhizome is a natural source of podophyllotoxin for etoposide and teniposide manufacture. The species is not listed on CITES, but wild-collected material should not be purchased. This is a further reason, alongside the toxicity, not to dispense the herb.

References

  1. Karuppaiya P, Tsay HS. Therapeutic values, chemical constituents and toxicity of Taiwanese Dysosma pleiantha – A review . Toxicology Letters (2015) [DOI]

This information is for educational purposes only and is not intended to replace professional medical advice. Always consult a qualified healthcare provider before using any herbal remedy, especially if you are pregnant, nursing, or taking medications.

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