Ku Shen
StarSophora flavescens Ait.
Traditionally used for
- Digestion
- Urinary & fluids
- Menstrual & women's health
- Skin
- Liver & jaundice
Cautions & contraindications
- Heart conditions
- Liver conditions
- Toxic — professional use only
☯ TCM Properties
Clears Heat and dries Dampness; Kills Parasites and Stops Itching; Promotes Urination; Disperses Wind
Traditional Chinese Uses
Ku Shen (苦参) is the root of Sophora flavescens Ait. (Fabaceae), Radix Sophorae Flavescentis. It is profoundly bitter and cold, entering the Heart, Liver, Stomach, Large Intestine and Bladder channels. It clears Heat and dries Dampness, kills parasites and stops itching, promotes urination, and disperses Wind.
Internally it treats Damp-Heat in the lower body: dysenteric disorders with blood and pus, jaundice, scanty painful urination, and Damp-Heat vaginal discharge. Its best-known use is external and dermatological — decocted as a wash or soak for eczema, weeping and itching skin lesions, scabies, tinea, genital itching and trichomonal infestation, where its parasiticidal and anti-pruritic actions are combined with its drying of Dampness.
It is one of the harshest cold, drying herbs in routine use and readily damages Stomach Qi; it is contraindicated where the Spleen and Stomach are deficient and cold, and is classically held to counteract Li Lu (Veratrum).
Western Herbalism Properties
Pharmacological Effects
- Antiarrhythmic: Root injection, total alkaloids (200 mg/kg i.v.), total flavones, matrine, oxymatrine and sophocarpine antagonized chemically induced arrhythmias in mice, rats, guinea pigs, rabbits, cats and dogs; flavones also in cultured rat myocardial cells.
- Other cardiovascular: Injection caused bradycardia, reduced contractility and prolonged P-R interval, increased coronary flow, lowered blood pressure and dilated ear and renal vessels in animals; vexibinol and kurarinone inhibited aortic contraction, suggesting Ca2+ channel blockade.
- Antiasthmatic, antitussive, expectorant: Fluid extract, decoction and alkaloids protected guinea pigs from histamine asthma (comparable to aminophylline); oral oxymatrine acts via conversion to matrine; sophocarpine antitussive; total flavones expectorant in mice.
- Antibacterial, antiinflammatory, antipyretic: Matrine inhibited Shigella, E. coli, Proteus, streptococci and S. aureus in vitro, reduced paw and ear inflammation in rats and was antipyretic in yeast-fevered rats.
- Leukopenia prophylaxis: Total alkaloids and oxymatrine (not matrine) were therapeutic in X-ray-induced leukopenia in rabbits.
- Antiulcerative: Oxymatrine and matrine reduced stress and other ulcers in rats; vexibinol 25-50 mg/kg oral inhibited ulcers and acid secretion.
- Antineoplastic and immunological: Matrine and oxymatrine active against sarcoma 180; sophocarpine inhibited several transplanted tumours and tumour DNA synthesis; matrine immunosuppressive in vitro.
- Other effects: Oxymatrine 3.6 mg/kg i.m. reduced CCl4 or galactosamine liver injury; diuretic effects reported but questionable.
Source: Zhu YP. Chinese Materia Medica: Chemistry, Pharmacology and Applications. Harwood Academic, 1998, p. 149.
Relationships
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Botanical Description
Sophora flavescens (Ku Shen, shrubby sophora) is a perennial subshrub or herbaceous perennial in the Fabaceae family, growing 50 to 150 centimeters tall from a long, cylindrical, yellowish woody taproot that constitutes the medicinal material. The erect, ridged, sparsely branched stems bear alternate, odd-pinnate leaves 20 to 25 centimeters long with 11 to 25 ovate to oblong-lanceolate leaflets 3 to 4 centimeters long, finely pubescent on the lower surface. From mid summer to early autumn, dense terminal racemes 15 to 25 centimeters long bear numerous pale yellow to cream papilionaceous flowers about 1.5 centimeters long, characteristic of the legume family. The legume pods are linear-cylindrical, 5 to 10 centimeters long, slightly constricted between the seeds, with a long beak. The bark of the root is yellowish-brown, the wood pale yellow and intensely bitter when chewed, giving rise to the Chinese name Ku Shen (bitter root). Native to East Asia, widely distributed across China, Korea, Japan, and Russia.
Active Constituents
Matrine
Quinolizidine (matrine-type) alkaloidThe principal alkaloid of the root and, with oxymatrine, the Chinese Pharmacopoeia assay marker: the two together must total at least 1.2 percent of the dried root. Matrine has anti-inflammatory, antiviral, antifibrotic, antiparasitic and sedative activity in preclinical work, but its serious adverse effects, chiefly hepatotoxicity and neurotoxicity, are the main factors limiting clinical use. Matrine cardiotoxicity has been traced experimentally to depletion of cysteine and glutathione with mitochondrial dysfunction and caspase-mediated apoptosis.
Oxymatrine
Quinolizidine alkaloid N-oxideThe N-oxide of matrine and the other Pharmacopoeia assay marker. It is largely reduced to matrine in vivo, so oxymatrine exposure carries matrine toxicity. Isolated oral oxymatrine, not Ku Shen decoction, is the form used in the chronic hepatitis B trial literature.
Sophoridine
Quinolizidine (matrine-type) alkaloidA matrine stereoisomer present in the root and quantified alongside matrine and oxymatrine in HPLC assays of Kushen. It has been reported to cause hepatotoxicity, neurotoxicity and cytotoxicity in cell and animal studies.
Sophocarpine
Quinolizidine (matrine-type) alkaloidAn unsaturated matrine analogue. In zebrafish embryos, sophocarpine and matrine altered spontaneous movement and impaired swimming at concentrations below those causing lethality or malformation, which is direct evidence of neurotoxic potential at sublethal exposure.
Kurarinone
Prenylated flavanoneA major prenylated flavonoid of Sophora flavescens and the constituent identified as the main hepatotoxic principle: it accumulates in rat liver and drives the hepatotoxicity of the extract. This is important because Ku Shen hepatotoxicity is often attributed to the alkaloids alone; the flavonoid fraction matters too, and alkaloid-standardised quality control does not control for it.
Kushenol series (kushenol A, I and congeners)
Prenylated flavonoidA large series of prenylated flavonoids characteristic of this species, linked in preclinical work to antimicrobial, antioxidant and antitumour activity. They are not covered by the Pharmacopoeia assay, so their content varies widely between batches.
Trifolirhizin
Pterocarpan glycosideA pterocarpan glycoside of the root reported to contribute to the antimicrobial and anti-inflammatory activity of Kushen extracts. Evidence is in vitro.
⚠ Drug Interactions
Theophylline and other CYP1A2 substrates (e.g. clozapine, tizanidine)
A rat study of whole Sophora flavescens extract found induction of hepatic cytochrome P450s with a measurable impact on theophylline elimination. Because theophylline has a narrow therapeutic index and its toxicity is dose-related in both directions, an unquantified induction effect is clinically significant. The evidence is animal, in this species, with the whole extract rather than isolated alkaloids.
Clinical note: Avoid concurrent use. If a patient on theophylline has already been taking Ku Shen, check a theophylline level before and after stopping the herb, since clearance may fall again on withdrawal.
Indinavir and other CYP3A4 or P-glycoprotein substrate antiretrovirals
In rats, Sophora flavescens reduced the oral exposure of indinavir, with the authors attributing the effect to CYP3A and P-glycoprotein. Oxymatrine contributed at least partly to the CYP induction, and Sophora flavescens induced CYP3A expression through activation of the pregnane X receptor. For protease inhibitors, even a modest fall in trough concentration can select resistance.
Clinical note: Do not combine Ku Shen with protease inhibitors or other antiretrovirals without specialist input. Ask HIV-positive patients directly about herbal use rather than waiting for them to volunteer it.
CYP2B6 substrates (efavirenz, bupropion, cyclophosphamide, methadone)
Matrine and oxymatrine dose-dependently induced the activity and gene expression of CYP2B1, the rat orthologue of human CYP2B6, with the effect attributed to constitutive androstane receptor activation. Matrine also slightly induced CYP2E1. These are rat data with isolated alkaloids, so the human magnitude is unknown.
Clinical note: Flag for any patient on a CYP2B6-dependent drug, particularly methadone, where induction can precipitate withdrawal.
Hepatotoxic drugs (paracetamol, methotrexate, isoniazid, azoles, statins)
Ku Shen hepatotoxicity is documented experimentally and mechanistically: kurarinone accumulates in rat liver and is identified as a major hepatotoxic constituent of the extract, and matrine and sophoridine are separately reported to cause hepatotoxicity. Matrine cardiotoxicity works partly through depletion of cysteine and glutathione via the ATF4/CTH pathway, and glutathione depletion is exactly the mechanism by which paracetamol injures the liver, so the two insults converge.
Clinical note: Do not use Ku Shen in a patient with existing liver disease or on other hepatotoxic drugs. Check liver function before starting prolonged courses and again at four to six weeks, and stop at the first unexplained transaminase rise.
Antiarrhythmics, beta-blockers and non-dihydropyridine calcium channel blockers (verapamil, diltiazem)
Acute Sophora alkaloid poisoning in Hong Kong, most often attributed to excessive doses of Sophora flavescens, presents with dizziness, vomiting and palpitation. Matrine cardiotoxicity has been demonstrated experimentally through reactive oxygen species accumulation, mitochondrial permeability transition pore opening, loss of mitochondrial membrane potential and caspase-9 and caspase-3 activation. Adding cardiodepressant drugs to a cardiotoxic alkaloid load has no supporting study but an obvious rationale.
Clinical note: Avoid in patients with conduction disease or on rate-limiting cardiac drugs, and keep strictly to Pharmacopoeia dosing. Palpitation or dizziness in a patient taking Ku Shen should be treated as possible alkaloid toxicity, not dismissed.
Veratrum nigrum (Li Lu)
Ku Shen is one of the shen-named herbs prohibited with Li Lu under the classical Eighteen Incompatibilities. No pharmacokinetic study supports the pairing being uniquely dangerous, but the underlying hazard is real independent of the classical rule: Veratrum steroidal alkaloids cause bradycardia, hypotension and violent vomiting, and combining them with a matrine-type alkaloid that is itself cardiotoxic and emetic stacks the same toxicity.
Clinical note: Observe the classical prohibition. Veratrum should not be in a modern prescription at all in most jurisdictions.
Substitution or confusion with Shan Dou Gen (Sophora tonkinensis) and Ku Dou Zi (Sophora alopecuroides)
All three drugs carry matrine, oxymatrine, sophocarpine and sophoridine, and acute Sophora alkaloid poisoning in Chinese medicine practice is commonly the result of an excessive alkaloid dose. Sophora tonkinensis root in particular is the Sophora most associated with alkaloid poisoning and has a considerably narrower margin than Kushen, so a mis-supplied or co-prescribed Sophora silently multiplies the alkaloid load on the prescription.
Clinical note: Check the botanical identity on the supplier certificate, not just the pinyin name, and add up the total matrine-type alkaloid burden across the whole formula rather than reviewing each herb independently.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| decoction | 4.5–9 g | Daily | — | — | 中国药典 2020 【用法与用量】4.5～9g。外用适量，煎汤洗患处。 【注意】不宜与藜芦同用。 【性味与归经】苦，寒。归心、肝、胃、大肠、膀胱经。 — Chinese Pharmacopoeia 2020, quoted verbatim; route and cautions preserved. Replaces a cleared category-filler value. |
Evidence Tier
Strong evidence · 6 studiesRecorded 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.
Systematic review / meta-analysis
1
1 verified · 0 unverified
Randomized controlled trial
0
Other clinical trial
0
Observational / case report
1
0 verified · 1 unverified
Show the study
In vitro / animal
4
3 verified · 1 unverified
Show 4 studies
- Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats
- Induction of Hepatic Cytochrome P450s by the Herbal Medicine Sophora flavescens Extract in Rats: Impact on the Elimination of Theophylline
- Impact of the Herbal Medicine Sophora flavescens on the Oral Pharmacokinetics of Indinavir in Rats: The Involvement of CYP3A and P-Glycoprotein
- Effects of Matrine and Oxymatrine on Catalytic Activity of Cytochrome P450s in Rats
Other / unclassified
0
Verified: design read from PubMed for a DOI that resolves to the cited paper Unverified: taken from the study's recorded description
Clinical Studies
Oral oxymatrine preparation for chronic hepatitis B: A systematic review of randomized controlled trials
Fifty-two randomised trials in 5227 participants of oral oxymatrine capsules or tablets in chronic hepatitis B, of which 51 entered meta-analysis. Oral oxymatrine was associated with statistically significant effects on clearance of HBV DNA, HBsAg and HBeAg. The important caveat for a Ku Shen monograph is that this is isolated oxymatrine, mostly in trials of uncertain methodological quality, and it is not evidence for a Sophora flavescens decoction.
Acute Sophora alkaloid poisoning in Hong Kong
A review of confirmed acute Sophora alkaloid poisonings, in which the cases were most often caused by an excessive dose of Sophora flavescens. Symptoms were described as generally mild and included dizziness, vomiting and palpitation. This is the best available human evidence for the toxicity of this specific species as used in Chinese medicine.
Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats
Rats given Sophora flavescens extract developed liver injury, and the prenylated flavanone kurarinone accumulated in liver tissue and was identified as a major hepatotoxic constituent. This locates a substantial part of Ku Shen hepatotoxicity in the flavonoid fraction rather than the alkaloids, which the Pharmacopoeia assay does not measure.
Induction of Hepatic Cytochrome P450s by the Herbal Medicine Sophora flavescens Extract in Rats: Impact on the Elimination of Theophylline
Sophora flavescens extract induced hepatic cytochrome P450 enzymes in rats and altered theophylline elimination. This is the primary experimental basis for treating Ku Shen as an enzyme inducer rather than assuming it is pharmacokinetically inert.
Impact of the Herbal Medicine Sophora flavescens on the Oral Pharmacokinetics of Indinavir in Rats: The Involvement of CYP3A and P-Glycoprotein
Sophora flavescens altered the oral pharmacokinetics of the protease inhibitor indinavir in rats, with the authors implicating induction of CYP3A and P-glycoprotein. It is the most directly relevant experiment for the antiretroviral interaction warning.
Effects of Matrine and Oxymatrine on Catalytic Activity of Cytochrome P450s in Rats
Matrine and oxymatrine given to rats for 14 days dose-dependently induced CYP2B1 activity and gene expression, with matrine also slightly inducing CYP2E1. This identifies which enzymes the isolated alkaloids affect, as distinct from the whole-extract studies, and underpins the CYP2B6 substrate warning.
⚠ Safety & Contraindications
- Heart conditions
- Liver conditions
- Toxic — professional use only
Contraindications
Its use is prohibited in patients with deficiency-cold of the spleen and stomach. It antagonizes Radix et Rhizoma Veratri Nigri ( li lu ).
Source: Xi S, Gong Y. Essentials of Chinese Materia Medica and Medical Formulas. Academic Press/Elsevier, 2017, pp. 46–50.
Side Effects
- Occasional mild dizziness, nausea, vomiting and constipation, usually resolving spontaneously.
Source: Zhu YP. Chinese Materia Medica: Chemistry, Pharmacology and Applications. Harwood Academic, 1998, p. 149.
⚠ Rule-Based Cautions
These entries come from the deterministic rule tables that gate Verscienta's formula tools — classical pair prohibitions, pregnancy and lactation contraindications, and dose ceilings.
Incompatibilities (十八反 / 十九畏)
- 十八反: Li Lu × Ku Shen — avoid combining with Li Lu / Veratrum
Historical Texts
Shen Nong Ben Cao Jing
Han dynastyBen Cao Gang Mu (Compendium of Materia Medica), Li Shizhen
Ming dynasty, 1596References
- Xirui He, Jiacheng Fang, Linhong Huang, Jinhui Wang, Xiaoqiang Huang. Sophora flavescens Ait.: Traditional usage, phytochemistry and pharmacology of an important traditional Chinese medicine . Journal of Ethnopharmacology (2015) [DOI]
- Longtai You, Chunjing Yang, Yuanyuan Du, Wenping Wang, Mingyi Sun, Jing Liu, Baorui Ma, Linnuo Pang, Yawen Zeng, Zhiqin Zhang, Xiaoxv Dong, Xingbin Yin, Jian Ni. A Systematic Review of the Pharmacology, Toxicology and Pharmacokinetics of Matrine . Frontiers in Pharmacology (2020) [DOI]
- Xia Li, Ziwei Tang, Li Wen, Cen Jiang, Quansheng Feng. Matrine: A review of its pharmacology, pharmacokinetics, toxicity, clinical application and preparation researches . Journal of Ethnopharmacology (2021) [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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