Mao Gen

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Ranunculus japonicus Thunb.

Not yet clinically reviewed

Family: Ranunculaceae Genus: Ranunculus Species: japonicus Pinyin: Mao Gen

Synonyms: Ranunculus japonicus Thunb., Ranunculus acris subsp. japonicus (Thunb.) Hultén

Traditionally used for

  • Cough & breathing
  • Digestion
  • Urinary & fluids
  • Pain & joints
  • Skin
  • Liver & jaundice

Cautions & contraindications

  • Pregnancy
  • Diabetes
  • Allergy risk
  • Toxic — professional use only
Moderate evidence · 4 studies

☯ TCM Properties

Category: clearing heat
Temperature: warm
Taste: pungent
Functions:

Absorbs pus

Traditional Chinese Uses

Mao Gen (毛茛) is the whole herb with root of Ranunculus japonicus Thunb. (Ranunculaceae), the East Asian buttercup, gathered in summer and autumn. It is acrid in flavour and warm in nature, and it is toxic. It promotes urination and resolves jaundice, reduces swelling and stops pain, disperses corneal opacity, checks malarial disorders, and kills parasites. It is used for jaundice, malarial disorders, scrofula and tuberculous lymphadenitis, stomach pain, pterygium and corneal opacity, and for painful obstruction of the joints.

This is principally an external, counter-irritant drug. The fresh plant contains protoanemonin — about 0.12 per cent of the fresh root — a powerful vesicant that raises blisters on contact with the skin; on drying it polymerises to anemonin, which is not irritant, so fresh and dried material do not behave alike. The classical application is blistering therapy (发泡疗法): the crushed fresh herb is applied over a point or a site until a blister forms, for malarial disorders, jaundice, scrofula, joint and bone tuberculosis, bronchial asthma, and abscesses that have not suppurated. The fresh root is applied topically for tuberculous lymph nodes. It is not a herb for routine internal decoction, and the fresh plant is toxic if swallowed.

Mao Gen (毛茛) must not be confused with Bai Mao Gen (白茅根, Rhizoma Imperatae), the rhizome of Imperata cylindrica. That is a sweet, cold herb given internally at 15 to 30 g to cool the Blood and stop bleeding — a wholly different drug with a wholly different safety profile.

Western Herbalism Properties

Actions:
diuretic

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Botanical Description

Mao Gen is the whole herb and root of Ranunculus japonicus Thunb. (Ranunculaceae), the East Asian buttercup — a perennial herb 30–70 cm tall with fibrous roots, erect branching stems, and long-stalked, palmately 3–5-parted basal leaves with toothed lobes. Bright glossy yellow, five-petalled flowers are borne on slender branches in spring and summer, followed by clustered flattened achenes. The fresh plant contains ranunculin, which on crushing releases the potent vesicant protoanemonin. It is a toxic, acrid, warm drug used almost entirely externally — the mashed fresh herb is applied to acupoints or lesions to raise a counter-irritant blister for malaria, jaundice, rheumatic pain, and swellings. Not to be confused with Bai Mao Gen (Imperata cylindrica), an unrelated sweet, cold blood-cooling grass.

Habitat:

Damp meadows, stream banks, ditch margins, and grassy slopes across lowland and montane East Asia.

Native Region: China, Japan, Korea, Russian Far East, Taiwan

Active Constituents

Ranunculin

Glucoside of a hydroxy-gamma-lactone (protoanemonin precursor)

The stable storage form of the vesicant, and the chemotaxonomic marker of the Ranunculaceae. Intact ranunculin is not itself an irritant. When fresh tissue is crushed, bruised or chewed, endogenous beta-glucosidase hydrolyses it to protoanemonin. This is the single most important chemical fact about Mao Gen: the herb's activity and its hazard are both created at the moment of crushing.

Protoanemonin

Unsaturated gamma-lactone

The vesicant proper. It is a potent irritant of skin, eye and mucosa that binds sulfhydryl groups and disrupts disulfide bonds, causing dermo-epidermal separation and bulla formation, and it inhibits DNA polymerase and raises free radical levels. It is what makes fresh Mao Gen a deliberate blistering agent when the mashed fresh herb is applied topically, and what makes internal use of the fresh herb unsafe. It is unstable and dimerises to anemonin.

Anemonin

Dimeric gamma-lactone (protoanemonin dimer)

The non-irritant dimer that protoanemonin spontaneously forms. It is the form that predominates once the plant has withered or been dried, which is why drying largely abolishes the blistering property. A Mao Gen preparation that has been dried is therefore not the same drug as the fresh mashed herb, and cannot be expected to raise a blister.

Berberine

Protoberberine isoquinoline alkaloid

Identified in Ranunculus japonicus by UPLC-ESI-LTQ-Orbitrap MS and quantified as one of nine bioactive markers. In the same study berberine significantly inhibited the migration of rheumatoid arthritis fibroblast-like synoviocytes, offering a mechanism for the herb's traditional use over arthritic joints.

Yangonin

Styryl-alpha-pyrone (kavalactone)

One of forty-five constituents first reported from R. japonicus in a 2021 LC-MS survey. Like berberine it significantly inhibited migration of rheumatoid arthritis fibroblast-like synoviocytes in vitro.

Total glycosides of Ranunculus japonicus

Mixed glycoside fraction (flavonoid and lactone glycosides)

The standardised fraction used in most of the modern pharmacology on this species, including the antimalarial and cardiovascular work. It is a fraction rather than a single compound and its composition varies with the plant part and extraction used.

⚠ Drug Interactions

Occlusive dressings, plasters and topical vehicles that increase skin contact time

Major Evidence: Probable

The blistering action of fresh Mao Gen is dose- and time-dependent exposure of skin to protoanemonin, and occlusion increases both. Case reports in the same genus show how far this can go: three patients who applied Ranunculus arvensis locally for knee pain sustained chemical burns, one requiring flap surgery, and in those cases the plant had even been boiled and cooled first, leading the authors to suggest protoanemonin may be more heat-resistant than assumed. Those cases used R. arvensis, not R. japonicus, but both species carry the same ranunculin-protoanemonin chemistry.

Clinical note: Never occlude a fresh Mao Gen application, never leave it beyond the short intended contact time, and never apply it to broken skin, mucous membranes, the eye or the face. Warn the patient that a burn deeper than the intended blister needs medical assessment, not another application.

Drugs applied to or absorbed through blistered skin (e.g. topical NSAIDs, lidocaine, corticosteroid creams)

Moderate Evidence: Theoretical

A protoanemonin blister removes the stratum corneum barrier by causing dermo-epidermal separation. Anything applied to the de-roofed blister base afterwards is absorbed far more completely than through intact skin, so a dose calibrated for intact skin can become a systemic dose.

Clinical note: Do not apply other topical medicines to the treated site while it is blistered or weeping. Dress it as a wound, not as a treatment field.

Systemic corticosteroids, immunosuppressants and drugs causing neutropenia

Moderate Evidence: Theoretical

Blistering therapy creates an open wound by design. In a patient on corticosteroids, DMARDs, biologics or cytotoxic chemotherapy, that wound heals slowly and is at raised risk of cellulitis, which is a poor trade for a symptomatic treatment.

Clinical note: Do not use blistering therapy in immunosuppressed patients, in diabetics with neuropathy or poor peripheral circulation, or in anyone with impaired wound healing.

Mao Zhua Cao (Ranunculus ternatus) - confusion between the two Ranunculus drugs

Major Evidence: Theoretical

Mao Gen and Mao Zhua Cao are different drugs from the same genus with similar-sounding pinyin names. Mao Gen is the fresh whole plant of R. japonicus, a ranunculin-bearing vesicant used externally; Mao Zhua Cao is the dried tuberous root of R. ternatus, taken internally by decoction and reported to have low acute oral toxicity. Supplying or substituting Mao Gen where Mao Zhua Cao is intended means administering protoanemonin-generating fresh tissue by mouth, with blistering of the mouth and gastrointestinal mucosa the expected consequence.

Clinical note: Order by binomial and by plant part. If a herb sold for internal use is fresh Ranunculus aerial tissue rather than a dried tuberous root, do not dispense it.

Dosage

Form Amount Frequency Duration Population Notes
topical Appropriate amount — — — No Chinese Pharmacopoeia 2025 monograph for this drug, so no pharmacopoeial dose is given here. EXTERNAL USE ONLY. *Ranunculus japonicus* is a vesicant: the fresh plant contains protoanemonin (about 0.12 per cent of the fresh root), which blisters skin on contact, and blistering is the intended effect in the classical 发泡疗法 application — the crushed fresh herb is laid on a point until a blister forms, then removed. It is not a herb for internal decoction and the fresh plant is toxic if swallowed. The stored value of 6-15 g as a decoction was filler and did not describe this drug at all. The previous value was generic filler generated from tcm_category and has been removed rather than replaced with an estimate.

Evidence Tier

Moderate evidence · 4 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

Antimalarial Effect of the Total Glycosides of the Medicinal Plant, Ranunculus japonicus

Hae-Soo Yun, Sylvatrie-Danne Dinzouna-Boutamba, Sanghyun Lee, Zin Moon, Dongmi Kwak, Man-Hee Rhee, Dong-Il Chung, Yeonchul Hong, Youn-Kyoung Goo (2021) Pathogens in vitro

An extract of the young stem of R. japonicus inhibited both chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum with IC50 values of 6.29 and 5.36 micrograms/mL, and showed potent activity against P. berghei in infected mice given the extract orally, with improved hepatic, renal and haematological parameters and no observed toxicity. The material tested was the young stem, which is eaten as a food in Korea, and not the fresh mashed whole plant used as a topical vesicant.

Analgesic and Anti-Inflammatory Effects of Ranunculus japonicus Extract

Bo-Jin Cao, Qing-Yu Meng, Nan Ji (1992) Planta Medica animal Verified: In vitro / animal

Parenterally administered Ranunculus japonicus extract inhibited acetic-acid writhing and raised hot-plate pain thresholds in mice, and inhibited carrageenan paw oedema in rats, xylene-induced ear swelling and acetic-acid-induced vascular permeability in mice, and granuloma formation in rats. The route was parenteral, so this does not validate either oral or topical dosing of the crude herb.

Integrated strategy of LC-MS and network pharmacology for predicting active constituents and pharmacological mechanisms of Ranunculus japonicus Thunb. for treating rheumatoid arthritis

Zhao-Yi Wang, Fu-Hao Chu, Nian-Nian Gu, Yi Wang, Dan Feng, Xia Zhao, Xue-Dan Meng, Wen-Ting Zhang, Chao-Feng Li, Yang Chen, Shuang-Shuang Wei, Zhi-Qiang Ma, Rui-Chao Lin, Chong-Jun Zhao, Di-Xin Zou (2021) Journal of Ethnopharmacology in vitro

Fifty-four constituents of R. japonicus were identified by UPLC-ESI-LTQ-Orbitrap MS, forty-five of them for the first time in this species, and nine were quantified for quality control. The extract and two of its constituents, berberine and yangonin, significantly inhibited migration of rheumatoid arthritis fibroblast-like synoviocytes after 24 hours. The paper describes R. japonicus explicitly as a topically applied herb, first recorded in Zhou Hou Bei Ji Fang and used for over 1800 years for malaria, ulcers, carbuncle, jaundice, migraine, stomachache, toothache and arthritis.

Inhibitory activities of Ranunculus japonicus Thunb. ethanol extract against hepatitis B virus

Minhui Luo, Zhuohang Chen, Miaoya Liu, Qian Liang, Ruilian Han, Zongsuo Liang, Zhuoming Ye, Kuancheng Liu (2022) Journal of Medical Virology in vitro

An ethanol extract of R. japonicus reduced hepatitis B e antigen production in cell culture without affecting core protein expression, by reducing the efficiency of viral capsid assembly and delaying conversion of relaxed-circular DNA from single-stranded DNA. Covalently closed circular DNA levels and formation efficiency fell significantly. This is cell-culture work only, with no dose translation to a human preparation.

⚠ Safety & Contraindications

  • Pregnancy
  • Diabetes
  • Allergy risk
  • Toxic — professional use only

Contraindications

It cannot be taken orally, and its use should be cautious in pregnant women, and prohibited in patients with damaged skin or allergy.

Source: Xi S, Gong Y. Essentials of Chinese Materia Medica and Medical Formulas. Academic Press/Elsevier, 2017, p. 416.

Historical Texts

Zhou Hou Bei Ji Fang

Jin dynasty
The earliest text to record Mao Gen, cited in modern reviews as the origin of a record of use running more than 1800 years. It is documented there as a topically applied herb for malaria, ulcers, carbuncle, jaundice, migraine, stomachache, toothache, eye inflammation and arthritis. The classical use is external application of the fresh plant, which is consistent with its chemistry: the active irritant is generated only when fresh tissue is crushed.

References

  1. Youn-Kyoung Goo. Therapeutic Potential of Ranunculus Species (Ranunculaceae): A Literature Review on Traditional Medicinal Herbs . Plants (2022) [DOI]
  2. Yun-Lei Dai, Qing-Zhi Liu, Jian Wang, Meng Sun, Feng-Jv Niu, Hao-Cheng Wei, Chang-Zheng Zhou, Li Zhang. The genus Ranunculus L. (Ranunculus) in Asia: a review of its botany, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations . Journal of Pharmacy and Pharmacology (2024) [DOI]
  3. Betelhem Sirak, Misgana Aragaw, Solomon Tadesse. Ranunculin, Protoanemonin, and Anemonin: Pharmacological and Chemical Perspectives . Current Medicinal Chemistry (2025) [DOI]
  4. Abdullah O. Kocak, Murat Saritemur, Kenan Atac, Sibel Guclu, Ibrahim Ozlu. A rare chemical burn due to Ranunculus arvensis: three case reports . Annals of Saudi Medicine (2016) [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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