Anemonastrum flaccidum

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Anemonastrum flaccidum

Not yet clinically reviewed

Family: Ranunculaceae Genus: Anemonastrum Species: flaccidum

Synonyms: Anemone laevigata, Anemone tagawae, Anemone flaccida var. anhuiensis, Anemone flaccida var. tagawae, Anemone baicalensis var. laevigata, Anemone flaccida var. hirtella, Anemone amagisanensis, Anemonoides flaccida, Anemone baicalensis subsp. flaccida, Anemone anhuiensis, Arsenjevia flaccida, Anemone flaccida var. semiplena, Anemonidium flaccidum, Anemone flaccida, Anemone weixiensis

Western Herbalism Properties

Actions:
anti-inflammatoryantimicrobial

Botanical Description

Anemonastrum flaccidum, the soft or flaccid windflower (basionym Anemone flaccida), is a perennial herb of the family Ranunculaceae found in damp montane woodland and shaded meadows across East Asia, including China, Japan, Korea and the Russian Far East. It spreads by slender horizontal rhizomes and often forms colonies. The basal leaves are long-stalked and palmately divided into three to five toothed, lobed segments with a thin, soft texture. Slender flowering stems rise to about 15 to 40 centimetres, bearing a whorl of three stalked leaf-like bracts below an open cluster of usually two to three flowers. Each flower has five (sometimes more) white, petal-like sepals surrounding numerous yellow stamens and a cluster of green carpels; true petals are absent. The fruits are small flattened achenes tipped by a short beak. The thickened underground rhizome is the part valued in traditional Chinese medicine.

Native Region: China South-Central, China Southeast, Japan, Kuril Is., Sakhalin

Active Constituents

Flaccidoside II

Oleanane-type triterpenoid saponin

Concentration: 28.1 percent of the crude triterpenoid saponin fraction of the rhizome

The single most abundant saponin of the drug and the species marker compound. It induces apoptosis in neurofibromatosis-associated malignant peripheral nerve sheath tumour cells through a MAPK and haem oxygenase-1 dependent route, and it carries much of the anti-inflammatory activity attributed to the crude saponin fraction.

Anhuienoside E

Oleanane-type triterpenoid saponin

Concentration: 9.5 percent of the crude saponin fraction of the rhizome

A secondary saponin of the rhizome, quantified alongside flaccidoside II when the crude fraction is standardised. Its individual pharmacology has not been separated from that of the fraction.

Glycoside St-I4a

Oleanane-type triterpenoid saponin

Concentration: 8.9 percent of the crude saponin fraction of the rhizome

One of the six saponins that together make up roughly two thirds of the standardised extract. It is used as a chromatographic reference point rather than studied in isolation.

Hemsgiganoside B

Oleanane-type triterpenoid saponin

Concentration: 6.2 percent of the crude saponin fraction of the rhizome

A minor constituent of the standardised saponin fraction, contributing to the overall oleanane load without a separately characterised action.

Hederasaponin B

Oleanane-type triterpenoid saponin

Concentration: 5.6 percent of the crude saponin fraction of the rhizome

A saponin shared with ivy and several other genera, which is why it is a poor identity marker for this drug even though it is a real constituent of it.

Saponin W3

Oleanane-type triterpenoid saponin

Concentration: Isolated compound from the rhizome; not routinely quantified in the crude fraction

The single compound shown to suppress osteoclast differentiation, blocking RANKL-driven activation of MAPK and NF-kappaB signalling in cell culture. It is the mechanistic bridge between the crude drug's traditional use for joint disease and the bone-sparing effects reported in arthritic rodents.

Oleanolic acid

Pentacyclic triterpene aglycone

Concentration: The aglycone released from essentially all of the drug's saponins

Transcriptome and proteome work found no transcripts for alternative triterpene synthases in this species, so oleanane is effectively the only aglycone skeleton present and oleanolic acid is what remains after the sugar chains are hydrolysed. It is mildly anti-inflammatory and hepatoprotective in its own right.

Ranunculin

Glucoside of a hydroxylated lactone (protoanemonin precursor)

Concentration: Not assayed in this species; reported across the genus and family rather than measured here

Listed because its absence has never been demonstrated for this species, not because it has been quantified in it. Ranunculin occurs widely in Anemone and the wider Ranunculaceae, and beta-glucosidase released by crushing or chewing converts it to protoanemonin, a volatile vesicant lactone that blisters skin and mucosa. Protoanemonin dimerises to the much less irritant anemonin, and drying the plant largely destroys the vesicant activity, which is why the dried rhizome is the article used.

⚠ Drug Interactions

Denosumab and bisphosphonates (alendronate, zoledronic acid)

Theoretical Evidence: Theoretical

The total saponin fraction and the isolated saponin W3 both block osteoclast differentiation by inhibiting RANKL-induced NF-kappaB, JNK and p38 MAPK activation. Denosumab is a monoclonal antibody against RANKL, so the herb and the drug converge on the same axis; bisphosphonates suppress the same cell type by a different route. Whether an oral decocted dose reaches osteoclasts at an active concentration in humans has never been measured.

Clinical note: There is no reported case of harm, and additive bone protection would in principle be the intended direction. Treat this as a reason to monitor rather than to avoid, and be aware of it if a patient on antiresorptive therapy is also taking a Di Wu preparation for joint pain.

Methotrexate and other conventional DMARDs

Theoretical Evidence: Theoretical

In collagen-induced arthritis in rats the crude saponin fraction reduced paw swelling and suppressed serum TNF-alpha and interleukin-6, in the same direction as conventional anti-rheumatic therapy; dexamethasone was the positive control in that work. No pharmacokinetic or pharmacodynamic interaction has been studied in humans.

Clinical note: The greater practical risk is not a chemical interaction but a patient reducing or stopping a DMARD because a herbal preparation seems to be helping. Ask directly about prescribed anti-rheumatic drugs and make clear the herb is not a substitute.

Other Ranunculaceae drugs (Bai Tou Weng, Wei Ling Xian, Mao Zhua Cao) and fresh undried plant material

Moderate Evidence: Possible

Ranunculin and its breakdown product protoanemonin are family-level constituents of the Ranunculaceae. Crushing or chewing fresh material liberates protoanemonin, which is a potent vesicant that inflames lips, oral mucosa, oesophagus, stomach and skin, with effects ranging from transient burning to ulceration and slow-healing blisters. No assay of ranunculin content has been published for this species specifically, which is a gap in the data rather than a clean bill of health. Triterpenoid saponins are separately irritant to gastric mucosa at high doses.

Clinical note: Use only properly dried rhizome; drying converts the vesicant precursor and is the reason the traditional article is dried. Do not apply fresh crushed rhizome to skin for long periods, and warn patients handling raw material to wear gloves. Take care when stacking several Ranunculaceae drugs in one formula, particularly for a patient with existing gastritis or reflux.

Non-steroidal anti-inflammatory drugs (ibuprofen, diclofenac, naproxen)

Theoretical Evidence: Theoretical

Triterpenoid saponins are surface-active and irritate gastric mucosa at higher doses, while NSAIDs impair mucosal prostaglandin defence. Both are likely to be taken together in exactly the population this herb is used for, namely patients with painful joint disease. This is a plausible pharmacodynamic overlap, not an observed interaction.

Clinical note: Give with food, keep to the lower end of the traditional dose in patients on regular NSAIDs, and reassess if dyspepsia develops.

Dosage Calculator

⚖ Dosage Calculator

A weight-based mathematical estimate for Anemonastrum flaccidum. Not a prescription.

Evidence Tier

Moderate evidence · 5 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

Crude triterpenoid saponins from Anemone flaccida (Di Wu) exert anti-arthritic effects on type II collagen-induced arthritis in rats

Liu Q, Zhu XZ, Feng RB, Liu Z, Wang GY, Guan XF, Ou GM, Li YL (2015) Chinese Medicine animal

Male Wistar rats with collagen type II-induced arthritis were given the crude saponin extract of the rhizome at 200 or 400 mg/kg/day orally for thirty days, against dexamethasone and saline controls. Paw oedema and redness fell dose-dependently, synovial hyperplasia and inflammatory infiltration were reduced on histology, and serum TNF-alpha and interleukin-6 were markedly suppressed. The paper also gives the composition of the fraction by HPLC, with flaccidoside II at 28.1 percent. This is the best-characterised efficacy study on the drug and it is still a rodent study of an extract, not of a decoction.

Total Saponin from Anemone flaccida Fr. Schmidt Prevents Bone Destruction in Experimental Rheumatoid Arthritis via Inhibiting Osteoclastogenesis

Liu C, Yang Y, Sun D, Wang C, Wang H, Jia S, Liu L, Lin N (2015) Rejuvenation Research animal

Extends the anti-inflammatory finding to the bone compartment: the total saponin fraction preserved bone in an experimental rheumatoid arthritis model, and the effect tracked with reduced osteoclast formation rather than with analgesia alone. Together with the cell work on saponin W3 it is the basis for the theoretical overlap with antiresorptive drugs.

Triterpenoid Saponin W3 from Anemone flaccida Suppresses Osteoclast Differentiation through Inhibiting Activation of MAPKs and NF-κB Pathways

Kong X, Yang Y, Wu W, Wan H, Li X, Zhong M, Su X, Jia S (2015) International Journal of Biological Sciences in vitro Verified: In vitro / animal

Identifies a single saponin, designated W3, as an inhibitor of RANKL-driven osteoclast differentiation, acting upstream through MAPK and NF-kappaB signalling. It converts the crude-fraction bone finding into a defined molecular mechanism, but is entirely cell-based.

Triterpenoid saponin flaccidoside II from Anemone flaccida triggers apoptosis of NF1-associated malignant peripheral nerve sheath tumors via the MAPK-HO-1 pathway

Huang Y, Han LT, Fang Y, Cao Y, Wu FH, Liu E, Mo GY (2016) OncoTargets and Therapy in vitro

The dominant saponin of the drug induced apoptosis in cell lines derived from neurofibromatosis type 1 associated malignant peripheral nerve sheath tumours, through MAPK signalling and haem oxygenase-1 induction. Of interest for mechanism only; there is no animal or human oncology work on this herb and nothing here supports clinical use in cancer.

Alcohol extracts from Anemone flaccida Fr. Schmidt treat rheumatoid arthritis via inhibition of synovial hyperplasia and angiogenesis

Rao Q, Zhao X, Wu F, Guo X, Xu Y, Yu H, Cai D, Zhao G (2023) Molecular Medicine Reports animal and in vitro Verified: In vitro / animal

Reports that the alcohol extract, rather than the isolated saponin fraction, reduces synovial hyperplasia and new vessel formation in arthritis models. A corrigendum was issued in 2024 correcting a duplicated control image in the cell migration figure; the authors state the correction does not alter the results or conclusions. Preclinical only.

Historical Texts

Gui Zhou Min Jian Yao Wu (Guizhou Folk Medicines)

Twentieth century provincial folk-drug survey
Earliest documented source for the drug name Di Wu. This herb has no classical materia medica pedigree: it does not appear in the Shen Nong Ben Cao Jing, the Ming Yi Bie Lu or the Ben Cao Gang Mu, and entered the written record only through the modern provincial surveys of folk medicine. Practitioners should treat its indications as regional folk practice rather than as classical doctrine.

Zhe Jiang Yao Yong Zhi Wu Zhi (Zhejiang Medicinal Plants)

Twentieth century provincial flora of medicinal plants
Gives the function as dispelling wind-damp and freeing the channels and sinews, with the main indications wind-damp impediment pain and traumatic injury. The plant is Anemone flaccida in the older nomenclature, Chinese plant name e zhang cao; the drug is the dried rhizome, 2 to 8 cm long and 0.2 to 1.2 cm across, brown to dark brown with visible nodes and root scars.

Chinese folk nomenclature of the drug

Modern, twentieth century onward
Recorded regionally as Di Wu, Wu Gong San Qi, Er Lun Cao, Er Lun Qi, Hei Di Lei and Jin Chuan Zhu, chiefly in Hunan, Sichuan and Guizhou. The name Wu Gong San Qi invites confusion with true San Qi, Panax notoginseng, which is an entirely unrelated drug.

Pharmacopoeia of the People's Republic of China

Current editions
Di Wu has no Pharmacopoeia monograph and no official assay, so no content specification governs commercial material. A total-saponin preparation of the rhizome was reported in 2016 to have reached phase III clinical trial in China for rheumatoid arthritis, but no trial registration and no published results were located, so that status should not be relayed to patients as evidence of efficacy.

References

  1. Zhan C, Li X, Zhao Z, Yang T, Wang X, Luo B, Zhang Q, Hu Y. Comprehensive Analysis of the Triterpenoid Saponins Biosynthetic Pathway in Anemone flaccida by Transcriptome and Proteome Profiling . Frontiers in Plant Science (2016) [DOI]
  2. Kong X, Wu W, Yang Y, Wan H, Li X, Zhong M, Su X, Jia S, Lin N. Total saponin from Anemone flaccida Fr. Schmidt abrogates osteoclast differentiation and bone resorption via the inhibition of RANKL-induced NF-κB, JNK and p38 MAPKs activation . Journal of Translational Medicine (2015) [DOI]
  3. Zhao L, Chen WM, Fang QC. Triterpenoid Saponins from Anemone flaccida . Planta Medica (1990) [DOI]
  4. Zhao L, Chen WM, Fang QC. Two New Oleanane Saponins from Anemone flaccida . Planta Medica (1991) [DOI]
  5. Sirak B, Aragaw M, Tadesse S. Ranunculin, Protoanemonin, and Anemonin: Pharmacological and Chemical Perspectives . Current Medicinal Chemistry (2025) [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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