Pu Yin

Star

Wikstroemia indica (L.) C.A.Mey.

Not yet clinically reviewed

Family: Thymelaeaceae Genus: Wikstroemia Species: indica Pinyin: Liao Ge Wang Pu Yin

Synonyms: Daphne indica L., Wikstroemia indica (L.) C.A.Mey., 了哥王, Liao Ge Wang

Indian stringbushSmall-leaf salago了哥王

Traditionally used for

  • Ears & hearing
  • Nose & throat
  • Cough & breathing
  • Digestion
  • Bowel health
  • Urinary & fluids
  • Menstrual & women's health
  • Skin

Cautions & contraindications

  • Pregnancy
  • Breastfeeding
  • Liver conditions
  • Kidney conditions
  • Toxic — professional use only
Moderate evidence · 5 studies

☯ TCM Properties

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

Dispels Heat, resolves toxicity, promotes urination, kills intestinal parasites and removes accumulations

Traditional Chinese Uses

Bitter and cold with definite toxicity, entering the Lung and Liver channels, Pu Yin (Radix Wikstroemiae) dispels Heat and resolves toxicity, promotes urination, disperses stagnation and reduces masses, and kills intestinal parasites. It is used for Heat-toxin and Phlegm-Heat conditions—pneumonia, bronchitis, mumps (parotitis), tonsillitis, mastitis, scrofula and lymph-node swelling, carbuncles and toxic sores—and for oedema with abdominal distension and for worm accumulation. Caution: this is a toxic herb. It must be prepared and long-decocted (often processed by prolonged boiling), used only in controlled dose (roughly 6–12 g decocted, boiled 3–4 hours), and is contraindicated in pregnancy, lactation and deficiency-cold. Overdose causes vomiting, abdominal pain, diarrhoea, throat swelling and respiratory difficulty; the fresh sap is a skin and mucosal irritant. It should be used only under qualified supervision.

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Botanical Description

Pu Yin (葡銀) is the root and root-bark (with some use of the whole root and leaf) of Wikstroemia indica (L.) C.A.Mey., the Indian stringbush or tie bush (Thymelaeaceae), the plant more widely known in Chinese medicine as Liao Ge Wang (了哥王). It is an evergreen shrub 0.5–2 m tall with smooth reddish-brown branchlets and tough, extremely fibrous bark that cannot be snapped by hand. The opposite, obovate to elliptic leaves are hairless and leathery; small tubular yellow-green flowers appear in short terminal clusters, followed by ovoid red-to-dark fleshy fruits. The root is dug year-round, and its bark is thick and strongly fibrous. Both root and bark contain irritant, toxic constituents.

Habitat:

Open hillsides, roadside thickets, grassy slopes, forest margins and rocky ground in warm subtropical to tropical lowlands and hills.

Native Region: China, Southeast Asia, South Asia

Active Constituents

Daphnane-type diterpenoid orthoesters

Daphnane diterpenoid orthoester

Concentration: twenty-one distinct daphnane diterpenoids were detected in the stems by LC-MS/MS, six of them major enough to isolate; content in root and root bark is not standardised and no pharmacopoeial limit exists

The class that makes this plant genuinely toxic rather than merely bitter and cold. Daphnane orthoesters are confined to the Thymelaeaceae and Euphorbiaceae, are potent protein kinase C activators, and are severe vesicants: contact with the sap or freshly cut root bark blisters skin and mucosa, and ingestion produces vomiting and bloody diarrhoea. The same activity underlies the antitumour and anti-HIV interest in the class. Their presence, not the coumarins or flavonoids, is the reason this drug is processed before use.

Daphnoretin

Bicoumarin (coumarin dimer)

The most-studied single constituent of the root bark and the most cytotoxic of fifteen compounds isolated from it, with an IC50 of 28.89 µmol/L against HeLa cells. It is markedly insoluble in water, which limits both absorption from a decoction and its pharmaceutical development. Cytotoxicity of this order is not selective for tumour cells and should be read as a toxicity signal as much as an anticancer one.

Wikstroflavone B

Biflavonoid

A biflavonoid isolated from this species that synergises with curcumin against nasopharyngeal carcinoma cells in vitro, suppressing proliferation, migration and invasion and blocking FAK and STAT3 phosphorylation. The evidence is cell-culture only.

Lignans and neolignans

Lignan / neolignan

Eight lignans and neolignans, two of them previously undescribed, have been isolated from the water-soluble fraction of the twigs and leaves. One reduced interleukin-1 beta secretion from LPS-stimulated RAW 264.7 macrophages with an IC50 of 9.73 µM, so part of the anti-inflammatory action of the aqueous extract is attributable to this polar, comparatively benign fraction rather than to the diterpenes.

⚠ Drug Interactions

Raw (unprocessed) Radix Wikstroemiae substituted for sweat-soaked processed material

Major Evidence: Established

This is a toxic drug that is used only after processing, and the two forms are not interchangeable. The oral LD50 of the raw root in rats is 4.05 g/kg against a clinical daily dose of about 0.029 g/kg, a margin of roughly 140-fold. After processing by the Miao 'sweat-soaking' method no LD50 could be established: the maximum tolerated dose was 20 g/kg and the minimum lethal dose 30 g/kg, 109 and 164 times the clinical daily dose. Proton NMR metabolomics of rat urine showed mitochondrial damage in hepatocytes and renal tubules with the raw drug and none with the processed drug, alongside falls of 48%, 44% and 65% in three toxic constituents. Both forms retained anti-inflammatory efficacy in collagen-induced arthritis.

Clinical note: Establish that the material is the processed drug before prescribing it, and treat unlabelled or self-collected root as raw. Never advise a patient to prepare this root themselves.

Hepatotoxic and nephrotoxic drugs (e.g. paracetamol, methotrexate, aminoglycosides, ciclosporin)

Major Evidence: Probable

Urinary metabolomics in rats given the raw root identified thirty-four altered metabolites and disturbances of energy, carbohydrate, amino acid, organic acid and lipid metabolism, with mitochondrial injury in hepatic and renal tubular cells and rises in the metabolic markers of hepatotoxicity and nephrotoxicity. Adding a drug cleared or concentrated by the same organs compounds the insult, and the herb's therapeutic margin is already narrow.

Clinical note: Avoid in existing liver or kidney impairment, keep courses short, and do not combine with drugs that require liver-function or renal monitoring in their own right. Check liver and renal function if use extends beyond a short course.

Direct skin, eye and mucosal contact when handling or preparing the raw root bark

Major Evidence: Established

Daphnane orthoester diterpenes are among the most potent plant vesicants known and act by protein kinase C activation rather than by simple chemical irritation, so the reaction is delayed and out of proportion to the amount contacted. The Qing dynasty materia medica already records the plant as lethal enough to kill dogs, and the drug's own tradition of processing before use exists to blunt exactly this class of compound.

Clinical note: Handle raw root and root bark with gloves, keep it away from the eyes and mucosae, and do not use it in the topical formulations for broken skin that the classical texts describe without accepting that a blistering reaction is the expected outcome.

Use in pregnancy and in women trying to conceive

Major Evidence: Probable

Wikstroemia indica is bitter, cold and explicitly toxic, and its diterpene class is shared with Yuan Hua (Daphne genkwa), a drug excluded from use in pregnancy throughout the Chinese tradition. No reproductive toxicology of Wikstroemia indica in any species has been published, so the position rests on the toxicity of the drug itself and of its chemical relatives rather than on data.

Clinical note: Do not prescribe in pregnancy or lactation, and take a pregnancy history before use in any woman of childbearing age.

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

1H‑NMR‑based metabolic profiling of rat urine to assess the toxicity‑attenuating effect of the sweat‑soaking method on Radix Wikstroemia indica

Zhou ZR, Feng G, Li LL, Li W, Wu ZG, Zheng CQ, Xu Q, Ren CC, Peng LZ (2022) Experimental and Therapeutic Medicine animal

Rats received raw or sweat-soaked Radix Wikstroemiae and their urine was profiled by proton NMR. Thirty-four metabolites were altered by the raw drug and thirty-two by the processed drug, with disturbance of energy, carbohydrate, amino acid, organic acid and lipid metabolism. Hepatic and renal tubular mitochondria were injured in the raw group but not the processed group, and markers of hepatotoxicity and nephrotoxicity fell after processing. The paper records an oral LD50 of 4.05 g/kg for the raw drug against a clinical daily dose of 0.029 g/kg, while the processed drug had a maximum tolerated dose of 20 g/kg and a minimum lethal dose of 30 g/kg. Three toxic constituents fell by 48%, 44% and 65% on processing.

Identification of Daphnane Diterpenoids from Wikstroemia indica Using Liquid Chromatography with Tandem Mass Spectrometry

Zhang M, Otsuki K, Takahashi R, Kikuchi T, Zhou D, Li N, Li W (2023) Plants in vitro

LC-MS/MS analysis of the stems of Wikstroemia indica detected twenty-one daphnane diterpenoids. Six major compounds were isolated and characterised by MS and NMR and the remaining fifteen were assigned by fragmentation analysis. This was the first disclosure of a structurally diverse daphnane diterpenoid profile in this species, and it establishes that the toxicologically important class is present in quantity in the aerial stems and not only in the root.

Study of the mechanism underlying the anti-inflammatory effect of Miao medicine comprising raw and processed Radix Wikstroemia indica using the “sweat soaking method”

Song X, Feng G, Ren C, Li W, Liu W, Liu G, Zhang J, Lei Y, He Z, Han C, Liu T, Ma K, Hou J (2024) Journal of Ethnopharmacology animal Verified: In vitro / animal

Raw and sweat-soaked Radix Wikstroemiae were compared in rats with collagen-induced arthritis using network pharmacology and NMR metabolomics of plasma and urine. Both forms reduced paw and ankle swelling, arthritis index and IL-1 beta, IL-6, TNF-alpha and nitric oxide, and both improved joint histopathology, with the shared pathways being steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism and tryptophan metabolism. The practical point is that processing removed toxicity without removing the anti-inflammatory effect.

Three new compounds from the dried root bark of Wikstroemia indica and their cytotoxicity against HeLa cells

Shi P, Liu Z, Cen R, Mao C, Han N, Yin J (2022) Natural Product Research in vitro

Fifteen compounds, three of them new, were isolated from the n-butanol fraction of a 70% ethanol extract of the dried root bark and screened against HeLa cells. Daphnoretin was the most cytotoxic, with an IC50 of 28.89 µmol/L. The work identifies daphnoretin as the dominant cytotoxic principle of the root bark, the part of the plant used medicinally.

Lignans and neolignans from the twigs and leaves of Wikstroemia indica (L.) C.A. Mey. with their effects on LPS-induced IL-1β and IL-10 secretion in RAW 264.7 macrophages

Nguyen VL, Cao VA, Nguyen TT, Tran TH, Hoang VD, Do TH (2025) Natural Product Research in vitro

Eight compounds, including two new neolignans, were isolated from the water-soluble fraction of the twigs and leaves. One lignan reduced interleukin-1 beta secretion from LPS-stimulated RAW 264.7 macrophages with an IC50 of 9.73 µM. The result matters mainly because it locates part of the anti-inflammatory activity in a polar fraction distinct from the toxic diterpenes.

Historical Texts

Sheng Cao Yao Xing Bei Yao

Qing dynasty (1711)
Earliest record of the drug, entered under the older name Jiu Xin Cai rather than Liao Ge Wang. The entry is a warning as much as an indication: the herb is toxic and can kill, it must not be taken carelessly, and it poisons dogs, a dog that eats it being certain to die.

Ling Nan Cai Yao Lu

Republican period (1932)
The first text to use the name Liao Ge Wang. It records mainly external use: the leaves pounded with salt and applied to disperse red and black stasis in the skin, draw out toxin and reduce swelling, the fruit applied to abscesses, and the root, called Du Chu Gen, steamed and sun-dried nine or ten times before being decocted in wine for severe traumatic injury.

References

  1. Shao M, Lou D, Yang J, Lin M, Deng X, Fan Q. Curcumin and wikstroflavone B, a new biflavonoid isolated from Wikstroemia indica, synergistically suppress the proliferation and metastasis of nasopharyngeal carcinoma cells via blocking FAK/STAT3 signaling pathway . Phytomedicine (2020) [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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