Sophora

Sophora: A Comprehensive Reference

1. Identity: Botanical Classification, Nomenclature, and Natural Source

Sophora is a genus of the Fabaceae (legume) family containing approximately 52 species, nineteen varieties, and seven forms, widely distributed in Asia, Oceania, and the Pacific islands, ranging in habit from herbaceous (Sophora flavescens Aiton) to trees (Sophora japonica L.). The two species of greatest medicinal and commercial importance are Sophora flavescens Aiton and Sophora japonica L., both of which bear distinct botanical identities, phytochemical profiles, and primary plant parts used.

1.1 Sophora flavescens Aiton (Kushen)

Sophora flavescens is a medicinal plant in the genus Sophora of the Fabaceae family. The root of S. flavescens is known in China as Kushen and has a long history of wide use in multiple formulations of Traditional Chinese Medicine (TCM). The plant is a herbaceous subshrub that is 0.5–1.5 m tall. The drug material used in medicine is Radix Sophorae Flavescentis, the dried root. In modern botanical nomenclature, the species is sometimes referenced under the synonym Sophora flavescens Ait.

1.2 Sophora japonica L. (Huai; Japanese Pagoda Tree / Chinese Scholar Tree)

Sophora japonica (Fabaceae), also known as Huai, is a medium-sized deciduous tree commonly found in China, Japan, Korea, Vietnam, and other countries. The use of this plant has been recorded in classical medicinal treatises of ancient China, and it is currently recorded in both the Chinese Pharmacopoeia and European Pharmacopoeia. The primary plant parts used are the flower buds and fruits, officially designated in the Chinese pharmacopoeial tradition as Flos Sophorae Immaturus (dried flower buds) and Fructus Sophorae (dried fruits). According to the European Pharmacopoeia (Ph. Eur. 9), the drug Sophorae japonicae flos immaturus is the whole flower buds of Styphnolobium japonicum (L.). The species is also referred to as Styphnolobium japonicum (L.) Schott in more recent taxonomic revisions.

1.3 Other Notable Species

Some of the most notable species in the genus include Sophora flavescens, Sophora japonica, and Sophora alopecuroides. Traditional Chinese medicine used more than 15 different species, including the famous species S. flavescens Ait. and S. japonica L., for the treatment of diarrhea and gastrointestinal disorders (S. flavescens), and hematuria, hemorrhoids, and hypertension (S. japonica).

1.4 Common Forms and Preparations

The extracts of S. flavescens are mainly used in compounds or as decoctions with other herbal products and are taken orally. Extracts are taken either orally or by injection. In the case of S. japonica, modern supplements commonly present Sophora japonica extract as rutin-standardised powders or capsules (for example, "Sophora japonica extract 95% rutin"), providing anywhere from about 100 mg to 500 mg rutin per capsule. The flowers are used phytotherapeutically as Sophorae japonicae flos, and in cosmetics as Sophora japonica flower extract, leaf extract, bud extract, and fruit extract (INCI designations).

2. Traditional and Historical Use

2.1 Sophora flavescens in Traditional Chinese Medicine

Sophora flavescens (Fabaceae), also known as Kushen, has been an important species in Chinese medicine since the Qin and Han dynasties. The root of Sophora flavescens has a long history in the traditional medicine of many countries, including China, Japan, Korea, India, and some countries in Europe. In TCM, Sophora flavescens has been used extensively, mainly in combination with other medicinal plants in prescriptions to treat fever, dysentery, hematochezia, jaundice, oliguria, vulvar swelling, asthma, eczema, inflammatory disorders, ulcers, and diseases associated with skin burns.

This observed traditional efficacy corresponds with its documented 2,000-year history of use in treating intestinal inflammation, as recorded in the Shennong Ben Cao Jing (ca. 100 CE), which explicitly describes its capacity to "clear heat, dry dampness, and relieve dysentery." Shennong's Materia Medica also recorded that Sophora flavescens could treat jaundice, lumps, and dysuria, and noted its effect of removing carbuncles and swelling.

The root of Sophora flavescens has been widely used for the treatment of symptoms such as fevers, dysentery, jaundice, vaginal itching with leukorrhagia, abscesses, carbuncles, enteritis, leukorrhea, pyogenic infections of the skin, scabies, swelling, and pain in different TCM formulations.

2.2 Traditional Administration Methods

In TCM practice, Ku Shen was prepared in several ways. The root of Sophora flavescens has a long history in the traditional medicine of many countries, including China, Japan, Korea, India, and some countries in Europe. In TCM, Sophora flavescens has been used extensively, mainly in combination with other medicinal plants in prescriptions. Water-based decoctions (煎剂) constituted the primary oral form. Radix Sophorae flavescentis is an ancient Chinese herb; the function of Radix Sophorae flavescentis, as described in the Chinese Pharmacopoeia 2005, is to remove heat and dampness, and treat jaundice and skin diseases such as colpitis, psoriasis, and eczema.

2.3 Sophora japonica in Traditional Chinese Medicine

The flower buds and fruits of S. japonica, also known as Flos Sophorae Immaturus and Fructus Sophorae in China, are most commonly used in Asia (especially in China) to treat hemorrhoids, hematochezia, hematuria, hematemesis, hemorrhinia, uterine or intestinal hemorrhage, arteriosclerosis, headache, hypertension, dysentery, dizziness, and pyoderma. The dried flower buds (Flos Sophorae Immaturus) and fruits (Fructus Sophorae) have been used for centuries to "cool the blood" and stop bleeding, especially from hemorrhoids, the intestines, and the uterus, as well as to help with hypertension and headaches.

In traditional pharmacopoeial dosing, typical adult daily doses listed in formal pharmacopoeias are in the approximate range of 5–10 g of dried flower buds (Flos Sophorae Immaturus) or 6–9 g of dried fruits (Fructus Sophorae), usually decocted in water and combined with other herbs in a formula. Treatment courses are often short to medium term, aimed at specific problems like bleeding hemorrhoids or intestinal bleeding, rather than indefinite daily use.

3. Key Constituents and Active Compounds

3.1 Overall Phytochemistry of the Genus

Chemical investigations of different species of Sophora showed the presence of alkaloids (quinolizidine), flavonoids, prenylated flavonoids, and isoflavonoids as major and most significantly important classes of compounds. More than 300 compounds have been isolated from the genus, among which the major ones are quinolizidine alkaloids, particularly matrine and oxymatrine, and flavonoids, particularly prenylated and isoprenylated flavonoids.

3.2 Alkaloids of Sophora flavescens

The root of S. flavescens is especially rich in quinolizidine alkaloids. Ku Shen contains a variety of matrine alkaloids, such as aloperine, cytosine, lehmannine, matrine, oxymatrine, oxysophocarpine, sophocarpine, sophoramine, and sophoridine, the flavonoid kushenol, and the saponin sophoraflavoside.

Matrine: Chemically, matrine is classified as a quinolizidine alkaloid with the molecular formula C₁₅H₂₄N₂O and a molecular weight of 248.36 Da. Matrine is a quinolizidine alkaloid isolated from the roots of Sophora flavescens (Kushen), Sophora tonkinensis, and Sophora alopecuroides (Kudouzi).

Oxymatrine: Matrine (C₁₅H₂₄N₂O) and oxymatrine (C₁₅H₂₄N₂O₂) are the main alkaloid components of Radix Sophorae Flavescentis. Both matrine and oxymatrine have been formally approved for pharmaceutical use: in 1998, matrine and oxymatrine were approved for the treatment of chronic hepatitis B in China.

3.3 Flavonoids of Sophora flavescens

The main flavonoids isolated from the roots of Sophora flavescens include isoxanthohumol, nor-kurarinone [(2S)-sophoraflavanone G], kurarinone, and kushenol I. The flavonoids sophoraflavonone G and kurarinone may be responsible for antioxidant effects, mediated through free-radical scavenging. These prenylated flavanones are characteristic of S. flavescens and contribute to both its biological activity and its hepatotoxic potential.

3.4 Flavonoids of Sophora japonica

Sophora japonica contains five main flavonoids: rutin, quercetin, isorhamnetin, genistein, and kaempferol. The rutin content in the flower buds is particularly high, at up to 30%. Rutin (= rutoside) is a quercetin-3-rhamnoglucoside (quercetin-3-(6α-L-rhamnopyranosyl)-β-D-glucopyranoside). The principal components of S. japonica include flavonoids, isoflavonoids, triterpene and its glycosides, alkaloids, phospholipids (PLs), amino acids, microelements, and polysaccharides.

The overall chemical composition of S. japonica is substantial: approximately 153 chemical compounds, including flavonoids, isoflavonoids, triterpenes, alkaloids, polysaccharides, amino acids, and other compounds, have been isolated from the leaves, branches, flowers, buds, pericarps, and/or fruits.

4. Established Mechanisms of Action

4.1 Matrine and Oxymatrine

The mechanism of action of matrine may involve: (1) regulation of cancer cell invasion, migration, proliferation, and cell cycle to inhibit tumor growth; (2) reduction of oxidized low-density lipoprotein and advanced glycation end products by exerting anti-inflammatory and antioxidant effects; (3) protection of brain damage and cortical neurons by regulating apoptosis; and (4) restoration of the intestinal barrier and regulation of the intestinal microbiota.

With respect to anti-inflammatory signaling, matrine can significantly reduce intracellular reactive oxygen species (ROS) production and further inhibit the activation of the MKKs/p38 MAPK signaling pathway, thereby suppressing oxidized low-density lipoprotein-induced inflammation.

For antiviral activity, oxymatrine may inhibit HBV replication in vitro by interfering with the process of packaging pre-genomic RNA into the nucleocapsid, or by inhibiting viral DNA polymerase activity. Animal studies have further suggested that matrine may prevent liver fibrogenesis by inhibiting platelet-derived growth factor (PDGF) synthesis and transforming growth factor beta-1 (TGF-β1) proliferation, and may inhibit hepatitis B virus replication by increasing Th1 cytokines and decreasing Th2 cytokines to trigger immune responses.

Matrine and oxymatrine have been shown to cause CYP2B induction but not CYP3A, possibly mediated by activation of the constitutive androstane receptor (CAR). A mechanistic study using cell-based gene reporter assays demonstrated that S. flavescens induced CYP3A expression through the activation of pregnane X receptor (PXR), and N-methylcytisine, an alkaloid constituent of S. flavescens, was identified as a potent PXR activator.

4.2 Flavonoids: Rutin and Quercetin (S. japonica)

Rutin (rutoside), the main constituent of pagoda tree flowers and buds, has been experimentally shown to have various effects: antioxidant, vasoprotective, and oedema-protective, among others. Rutin inhibits the enzymes lipoxygenase and cyclooxygenase. However, bioavailability is low when rutin is ingested.

Biochanin A, irisolidone, genistein, and tectoridin from Sophora japonica were found to be stronger inhibitors of arachidonic acid- and thromboxane A₂-induced platelet aggregation compared with acetylsalicylic acid in rats. Quercetin from Sophora japonica inhibited free calcium accumulation within platelets, thereby preventing platelet aggregation.

4.3 Anticancer Signaling

Matrine and oxymatrine have been identified as primary anticancer alkaloids, exerting effects through induction of apoptosis, autophagy, ferroptosis, and inhibition of proliferation, invasion, and angiogenesis. Flavonoids like kurarinone also demonstrate anticancer potential by modulating PI3K/Akt and MAPK signaling pathways, while sophoridine has shown efficacy in suppressing tumor growth and metastasis in preclinical models.

The antitumor mechanisms of S. flavescens flavonoids are primarily attributed to apoptosis induction, modulation of oxidative stress, and regulation of multiple signaling pathways, including the PI3K/Akt pathway and the cAMP/PKA pathway.

4.4 Anti-inflammatory Mechanisms (Sophoraflavonone G)

Anti-inflammatory effects of sophoraflavonone G are attributed to inhibition of prostaglandin E₂ formation via COX-2 downregulation.

4.5 Vasodilatory Effects

S. flavescens flavonoids may promote vasodilation by inhibiting Ca²⁺ influx through a voltage-gated channel.

5. Scientific Evidence by Area of Use

5.1 Chronic Hepatitis B Virus (HBV) Infection

This is one of the most studied clinical applications of Sophora alkaloids. In 1998, matrine and oxymatrine were approved for the treatment of chronic hepatitis B in China. There are increasing laboratory and clinical studies on matrine and oxymatrine in treating chronic hepatitis B, and even liver cirrhosis.

A key randomized controlled trial (RCT) evaluated oxymatrine capsules against placebo. A randomized double-blind and placebo-controlled multicenter trial was conducted, with injection of oxymatrine used as a positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 weeks; 108 received capsule oxymatrine, 36 received injection of oxymatrine, and 72 received placebo. In the capsule-treated patients, 76.47% became normal in ALT level, and 38.61% and 31.91% became negative in HBV DNA and HBeAg, respectively. Oxymatrine extracted from Sophora alopecuraides L. has been shown to have a remarkable HBV-suppressing effect with a 40% serum conversion rate for HBeAg and HBV DNA, similar to that of alpha interferon.

A Cochrane-style systematic review evaluated this evidence base. The benefits and harms of Radix Sophorae flavescentis have never been established in systematic reviews with rigorous and reasonable methodology, noting that published reviews may have been limited by focusing only on specific subgroups or by assessing only certain outcomes. For hepatitis B cirrhosis, pharmacologic studies have demonstrated that oxymatrine (OM) exhibits anti-hepatitis B virus (HBV) and antifibrosis effects, and an increasing number of clinical controlled studies have found that OM combined with conventional therapy could improve the curative effect and reduce adverse events incidence in treating hepatitis B cirrhosis.

Evidence strength: There is moderate evidence from RCTs supporting oxymatrine's antiviral activity against HBV, including a significant multicenter double-blind trial. However, the overall body of clinical evidence is methodologically limited, and a Cochrane protocol has flagged the need for more rigorously designed trials. Effects are more clearly established for biomarker outcomes (ALT normalization, HBeAg seroconversion) than for hard clinical endpoints.

5.2 Oncology (Antitumor Applications)

Sophoridine hydrochloride injection has been approved as an anticancer drug in China. Clinical studies have reported that Kushen alkaloids are efficacious in the treatment of various types of solid tumors (including tumors of the lung, liver, and gastrointestinal tract). The treatment responses were reported to be comparable to, or better than, those of chemotherapy drug-treated patients. Kushen alkaloids demonstrate a good safety profile in cancer patients, such as reduced toxicity in bone marrow when used in combination with chemotherapeutic agents. However, long-term survival data for Kushen alkaloid-treated cancer patients remain to be demonstrated with well-controlled clinical studies and large patient cohorts, and studies on the mechanisms of action are limited.

At the mechanistic level, matrine (MT) and oxymatrine (OMT), two alkaloid components found in the roots of Sophora species, have various pharmacological activities and are demonstrated to have anti-inflammatory, anti-allergic, antiviral, anti-fibrotic, and cardiovascular protective effects. They have recently been proved to have anticancer potentials, such as inhibiting cancer cell proliferation, inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis, inducing cell differentiation, inhibiting cancer metastasis and invasion, reversing multidrug resistance, and reducing chemotherapy- or radiotherapy-induced toxicity when combined with other chemotherapeutic drugs.

Evidence strength: Preclinical (in vitro and animal) data are extensive. Formal human clinical evidence is limited; much derives from Chinese clinical reports rather than large, multi-center randomized trials with standardized endpoints. Long-term survival data are lacking.

5.3 Inflammatory Bowel Disease (Ulcerative Colitis)

Preliminary findings from several clinical studies suggest that Kushen extract or its formulations demonstrate potential therapeutic efficacy in alleviating symptoms in patients with inflammatory bowel disease (IBD). An RCT on the efficacy of Sophora compared with mesalazine in 126 patients with ulcerative colitis found evidence that therapy with Sophora may be beneficial in this condition.

Evidence strength: Preliminary clinical signals are present, but evidence remains limited by small trial sizes and the need for rigorous comparative data. This area requires further well-controlled trials.

5.4 Skin and Dermatological Conditions (Eczema, Pruritus)

The use of Sophora preparations for skin conditions is one of the oldest documented traditional applications. In terms of mechanistic evidence, matrine dose-dependently (at 50 or 10 mg/kg, applied for 22 days to dorsal skin) remarkably decreased serum levels of TNF-α and IL-4 and significantly alleviated skin lesions in animal models of eczema. Oxymatrine (OMT) imparts antipruritic effects and has been shown to effectively reduce symptoms of pruritus caused by histamine and chloroquine in acute and chronic eczema models in a dose-dependent manner.

With respect to antimicrobial applications relevant to skin infections: sophoraflavanone G and kurarinone showed significant antibacterial activity and anti-multidrug resistance properties. Mechanistic studies showed that they could target the bacterial membrane and cause destruction of membrane integrity and biosynthesis, inhibit cell wall synthesis, and disrupt bacterial biofilms, as well as interfere with the energy metabolism of methicillin-resistant Staphylococcus aureus.

Sophora flavescens is used to treat skin disorders in traditional medicine, but this use has not been proven in clinical trials. The Memorial Sloan Kettering Cancer Center's integrative medicine database notes this directly.

Evidence strength: Strong traditional use and preclinical (in vitro/animal) evidence for anti-inflammatory and antipruritic effects. Human clinical evidence specifically for eczema or pruritus from Sophora is limited and not yet conclusive.

5.5 Cardiovascular and Cerebrovascular Applications

Sophora japonica reduces cerebral infarction partly as a result of its anti-oxidative and anti-inflammatory activities. Previous studies found that Sophora japonica reduced the size of cerebral infarction and neurological deficits and reduced microglial activation, interleukin-1β release, and the number of apoptotic cells in ischemia-reperfusion injured Sprague-Dawley rats.

Administration of Sophora japonica decoction into the jugular veins of rabbits decreased cardiac muscle contractility and reduced heart rate, suggesting that Sophora japonica reduced the consumption of oxygen to protect cardiac function.

Evidence strength: These findings are from animal (in vivo) studies. There is currently no substantive body of human clinical trial evidence specifically for Sophora preparations in cardiovascular or cerebrovascular outcomes. Mechanistic plausibility is established in preclinical models only.

5.6 Antiviral Activity (Non-HBV)

In animal models, the antiviral properties of sophoridine, an alkaloid constituent, appear to be mediated via upregulation of IL-10 and IFN-gamma cytokines. Limited evidence suggests that a compound from Sophora flavescens may be useful for hepatitis B and coxsackie B viruses, but more data are necessary to support this use.

Evidence strength: Preliminary and largely in vitro or animal-based. Clinical evidence for antiviral indications beyond hepatitis B is insufficient to draw conclusions.

6. Body Systems and Health Areas Associated with Sophora

• Hepatic/Gastrointestinal system: Flavonoids and isoflavonoids from S. japonica exhibit a wide range of biological activities in vitro and in vivo, including anti-inflammatory, antibacterial, antiviral, anti-osteoporotic, antioxidant, radical scavenging, antihyperglycemic, antiobesity, antitumor, and hemostatic effects.
• Vascular and hematological system: Flower buds and fruits of S. japonica are used in Asia to treat hemorrhoids, hematochezia, hematuria, hematemesis, hemorrhinia, uterine or intestinal hemorrhage, arteriosclerosis, and hypertension.
• Immune and inflammatory system: Both matrine and oxymatrine modulate cytokine signaling, NF-κB, and MAPK inflammatory cascades, as documented in preclinical literature.
• Dermatological system: Traditional and preclinical evidence supports use for eczema, itching, pyogenic skin infections, and scabies.
• Oncology: Sophoridine is approved as an anticancer drug in China; matrine and oxymatrine show broad preclinical antitumor activity across multiple cancer types.
• Antiparasitic: Kushen has documented antiparasitic activity and diuretic effects, alongside modern pharmacological studies confirming its anti-inflammatory, antitumor, and analgesic properties.

7. Dosage Forms and Dosages Reported in Studies

In the pivotal hepatitis B multicenter RCT, patients received capsule oxymatrine or injection of oxymatrine over a 24-week treatment period; the study included 108 capsule-treated patients, 36 injection-treated patients, and 72 placebo patients. The precise milligram dosage of oxymatrine capsule used in that trial is not fully stated in available sources.

For S. japonica in traditional pharmacopoeial use, typical adult daily doses listed in formal pharmacopoeias are in the approximate range of 5–10 g of dried flower buds (Flos Sophorae Immaturus) or 6–9 g of dried fruits (Fructus Sophorae), usually decocted in water and combined with other herbs in a formula.

In animal eczema research, matrine was studied at doses of 50 or 10 mg/kg applied for 22 days to dorsal skin.

In the herb-drug interaction study involving indinavir, concomitant oral administration of Sophora extract at 0.158 g/kg or 0.63 g/kg and indinavir at 40 mg/kg in rats twice a day for 7 days resulted in a dose-dependent decrease in plasma indinavir concentrations, with 55%–83% decrease in AUC and 38%–78% reduction in C_max.

In hepatotoxicity studies in rats, Sophora flavescens extract (ESF) impaired hepatic function and caused fat accumulation in the liver after oral administration at doses of 1.25 and 2.5 g/kg for 14 days.

For modern dietary supplements, rutin-standardised capsules typically provide anywhere from approximately 100 mg to 500 mg rutin per capsule. In China, the flower buds and fruits of Sophora japonica are monographed in the Chinese Pharmacopoeia. In the European Union, rutin and quercetin are approved for use in food supplements and cosmetic products. In the United States, rutin is monographed in the NF11, and both rutin and quercetin are generally recognized as safe (GRAS) for use in food and dietary supplements.

8. Safety Considerations and Drug Interactions

8.1 Hepatotoxicity

Hepatotoxicity is the most clinically significant safety concern for S. flavescens. Hepatotoxicity, developmental toxicity, and neurotoxicity have sparked intense debate and research into the security of matrine. Among active components, matrine is considered a major active component; however, accumulating evidence suggests it may induce hepatotoxicity, leading to adverse events and imposing limitations on its clinical safety.

Sophora flavescens was indicated as the hepatotoxic ingredient of Zhixue capsules, which were recalled from the market because of serious hepatotoxic adverse events. Kurarinone, a flavonoid aglycone, was identified as the major hepatotoxic constituent of Sophora flavescens, and hepatic accumulation of kurarinone was detected.

Isoxanthohumol (IXN), a component of Sophora flavescens, enhances NLRP3 inflammasome activation by promoting the accumulation of ATP-induced mitochondrial reactive oxygen species (mtROS) and ASC oligomerization, indicating that IXN may be a risk factor for liver injury caused by the clinical use of Sophora flavescens.

Despite the generally low toxicity of S. flavescens flavonoids overall, certain specific compounds may induce hepatotoxicity, particularly with long-term or high-dose administration. For instance, sophoraflavanone G exhibits more pronounced hepatotoxicity compared to kushenol Z, which is closely related to their inherent structural properties.

8.2 Neurotoxicity and Developmental Toxicity

A large number of studies have shown that matrine has significant hepatotoxicity, neurotoxicity, and developmental toxicity. At high concentrations (>140 mg/L, 72 hours), matrine has been reported to attenuate albumin secretion by hepatocytes and induce the protein expression of CYP2A6, CYP2B6, and CYP3A4.

8.3 Herb-Drug Interactions: CYP450 and P-Glycoprotein

Sophora flavescens exhibits documented interactions with cytochrome P450 enzymes. The roots of Sophora flavescens showed that increased oxidative activities were associated with the elevation of protein levels of CYP1A2, CYP2B1/2, CYP2C11, and CYP3A. In patients taking Sophora flavescens, possible P450 induction-induced drug interactions should be noted to decrease the risk of therapeutic failure or adverse effects resulting from the use of additional therapeutic agents.

The interaction with the antiretroviral drug indinavir is particularly well-characterized. The herb-drug interactions between S. flavescens and indinavir, a protease inhibitor for HIV treatment, were evaluated in rats. Concomitant oral administration of Sophora extract (0.158 g/kg or 0.63 g/kg) and indinavir (40 mg/kg) twice a day for 7 days resulted in a dose-dependent decrease in plasma indinavir concentrations, with 55%–83% decrease in AUC and 38%–78% reduction in C_max. The CL/F increased up to 7.4-fold in Sophora-treated rats.

These findings suggest that there may be potential herb-drug interaction when S. flavescens is used, especially in conditions involving the prescription of multiple medicinal compounds, for example in HIV infection and AIDS treatment regimens.

8.4 Estrogenic Activity

Sophora flavescens has estrogenic effects and may stimulate the proliferation of hormone-sensitive cancer cells. This interaction is noted by the Memorial Sloan Kettering Cancer Center's integrative medicine database.

8.5 Antibiotic Interactions

In laboratory research, one of the compounds in Sophora flavescens increased the activity of ampicillin/gentamicin against oral bacteria, though clinical relevance has yet to be determined.

8.6 Limitations of the Evidence Base

There is currently a lack of systematic and in-depth understanding of Kushen extract's toxicity-efficacy relationship. This ambiguity surrounding the relationship not only poses multifaceted challenges for clinical practice and patient safety but also hinders the development of safer and more effective derivatives from Kushen. Investigating this toxicity-efficacy relationship and its underlying mechanisms possesses significant scientific importance and offers profound clinical value.

References

• Locke et al. "Local and traditional uses, phytochemistry, and pharmacology of Sophora japonica L.: A review." Journal of Ethnopharmacology, 2016. PubMed PMID: 27085938
• Xiao et al. "Sophora flavescens Ait.: Traditional usage, phytochemistry and pharmacology of an important traditional Chinese medicine." Journal of Ethnopharmacology, 2015. ScienceDirect
• Liu et al. "Ethnomedicinal uses, phytochemistry and bioactivities of Sophora flavescens Ait.: A review." Journal of Herbal Medicine, 2023. ScienceDirect
• Ibrahim et al. "The pharmacology of the genus Sophora (Fabaceae): An updated review." Phytomedicine, 2019. ScienceDirect
• Zhang et al. "Chromosomal level genome assembly of medicinal plant Sophora flavescens." Scientific Data / PMC, 2023.
• Cochrane/PMC. "Sophorus species for chronic hepatitis B virus infection." PMC6513607.
• Cochrane Review Protocol. "Radix Sophorae flavescentis for chronic hepatitis B." PMC6513334.
• Yang et al. "Oxymatrine therapy for chronic hepatitis B: A randomized double-blind and placebo-controlled multi-center trial." PMC4656524.
• Cochrane Review. "Radix Sophorae flavescentis versus no intervention or placebo for chronic hepatitis B." PMC6446139.
• Li et al. "Oral oxymatrine for hepatitis B cirrhosis." PMC6310577.
• Review. "Research progress on the pharmacological effects of matrine." PMC9469773.
• Wang et al. "Matrine: A Promising Natural Product With Various Pharmacological Activities." PMC7232545.
• Liu et al. "Matrine: Bioactivities and Structural Modifications." PubMed PMID: 27150374.
• Liu et al. "Anti-tumor activities of matrine and oxymatrine: literature review." Tumor Biology, 2014. Springer.
• Zhang et al. "Effects of Sophora japonica flowers (Huaihua) on cerebral infarction." PMC2954919.
• Li et al. "Impact of the Herbal Medicine Sophora flavescens on the Oral Pharmacokinetics of Indinavir in Rats: The Involvement of CYP3A and P-Glycoprotein." PMC3281083.
• Ueng et al. "Induction of Hepatic Cytochrome P450s by the Herbal Medicine Sophora flavescens Extract in Rats: Impact on the Elimination of Theophylline." ScienceDirect, 2015.
• Wang et al. "Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats." PMC6150336.
• Pubmed. "Isoxanthohumol, a component of Sophora flavescens, promotes the activation of the NLRP3 inflammasome and induces idiosyncratic hepatotoxicity." PMID: 34740771.
• PMC. "Chemical composition, antitumor properties and underlying mechanism of Sophora flavescens flavonoids: A review." PMC13069629.
• PMC. "Anti-Cervical Cancer Role of Matrine, Oxymatrine and Sophora Flavescens Alkaloid Gels and its Mechanism." PMC5929079.
• PMC. "Compound Radix Sophorae Flavescentis exerts antitumor effects by inhibiting the proliferation and inducing the apoptosis of esophageal carcinoma TE-8 cells." PMC4579809.
• Frontiers in Pharmacology. "Matrine in cancer therapy: antitumor mechanisms and nano-delivery strategies." 2025.
• Frontiers in Immunology. "Evaluation of the safety and efficacy of Sophorae Flavescentis Radix extract in the treatment of inflammatory bowel disease based on zebrafish models." 2025.
• Memorial Sloan Kettering Cancer Center. "Sophora flavescens." Integrative Medicine Herb Database.
• Altmeyer's Encyclopedia of Dermatology. "Sophora japonica." Phytotherapy entry.
• Altmeyer's Encyclopedia of Dermatology. "Sophorae japonicae flos immaturus." Phytotherapy entry.
• PubMed. "Main flavonoids from Sophora flavescens." PMID: 18956776.
• PMC. "Inhibition of hepatitis B virus by oxymatrine in vivo." PMC4688700.
• PMC. "Matrine inhibits IL-1β secretion in primary porcine alveolar macrophages through the MyD88/NF-κB pathway and NLRP3 inflammasome." PMC6626430.
• PMC. "Potential Pharmaceutical Applications of Quercetin in Cardiovascular Diseases." PMC9412669.