Coptis japonica
StarCoptis japonica
Also known as: Ōren黄連 オウレン · Kampo; Hwangnyeon黃連 황련 · Korean; Hoàng liên · Vietnamese
Traditionally used for
- Eye health
- Teeth & mouth
- Bowel health
Cautions & contraindications
- Pregnancy
- Young children
Western Herbalism Properties
Traditional Uses
In Japanese kanpō medicine the dried rhizome of Coptis japonica, known as ōren (黄連), is one of the principal source crude drugs for huáng lián, listed in the Japanese Pharmacopoeia. It is taken as a bitter cold remedy for diarrhoea, gastroenteritis, mouth ulcers and conjunctivitis and is a component of classical formulas such as Ōren-gedoku-tō (黄連解毒湯) and Hangeshashin-tō; the berberine-rich rhizome is also used in modern Japanese pharmacy as an antimicrobial bitter (Japanese Pharmacopoeia, 17th ed.; Tsumura kampō materia medica).
Botanical Description
Coptis japonica (Ranunculaceae), known in Japan as ōren (オウレン) and in Chinese herbal practice as one of the accepted sources of huáng lián, is a small evergreen perennial herb of cool, humid mountain forests in Japan and adjacent East Asia. It grows 10–25 cm tall from a slender, branched yellow rhizome that is intensely bitter and produces a brilliant yellow dye when broken. The basal leaves are long-petiolate, ternately or biternately compound, leathery and glossy dark green, with sharply incised and toothed leaflets. In early spring, slender scapes bear one to several small white to greenish-white flowers with five to seven petaloid sepals and narrow nectariferous petals. The fruit is a whorl of stipitate follicles. The bright yellow colour of the rhizome reflects a high content of the alkaloid berberine, along with coptisine and palmatine.
Active Constituents
Berberine
Protoberberine alkaloidConcentration: Dominant alkaloid of the rhizome and the marker compound on which Coptis rhizome is assayed
Berberine carries most of the drug's measurable pharmacology and essentially all of its interaction risk. It is a substrate of the hepatic uptake transporter OCT1 and of CYP2D6, has low oral bioavailability, and inhibits enzymes and transporters that handle co-administered drugs. It is also the compound behind the drug's antimicrobial reputation and behind its contraindication in jaundiced newborns.
Coptisine
Protoberberine alkaloidConcentration: Second major protoberberine of the rhizome; quantified alongside berberine in comparative assays of Coptis species
Coptisine was first characterised as a new alkaloid from this species in 1926. It bears a methylenedioxyphenyl group that CYP1A2, CYP2D6 and CYP3A4 convert to a reactive quinone-like metabolite, and it accumulates in liver through OCT1-mediated uptake; both mouse and human hepatocytes and whole mice show coptisine-induced hepatotoxicity. It is the alkaloid that makes Coptis a liver-relevant rather than a merely bitter drug.
Magnoflorine
Aporphine alkaloidConcentration: One of ten alkaloids quantified in Coptis japonica rhizome by UHPLC-QQQ-MS/MS; one of three alkaloids that separate the four Coptis rhizome species
A quaternary aporphine rather than a protoberberine. Together with jatrorrhizine and columbamine it is the chemical marker that distinguishes Coptis japonica rhizome from Coptis chinensis, Coptis deltoidea and Coptis teeta, which is why the Japanese and Chinese Coptis drugs cannot be treated as chemically identical.
Jatrorrhizine
Protoberberine alkaloidConcentration: Quantified in Coptis japonica rhizome; one of the three differential alkaloids across the four Coptis rhizome species
A minor protoberberine whose content varies systematically between Coptis species, making it useful for authentication. Like berberine it is poorly absorbed orally and undergoes extensive first-pass handling.
Columbamine
Protoberberine alkaloidConcentration: Quantified in Coptis japonica rhizome; one of the three differential alkaloids across the four Coptis rhizome species
A demethylated congener of palmatine that, with jatrorrhizine and magnoflorine, differentiates the source species of Coptis rhizome. It is a minor constituent and not an assay marker in its own right.
Palmatine and epiberberine
Protoberberine alkaloidsConcentration: Quantified alongside berberine and coptisine in Coptis japonica rhizome
Both correlate positively with the astringency and aftertaste that traditional practice uses to judge Coptis quality, which is the empirical basis for grading the drug by taste. Epiberberine, coptisine, berberine and palmatine together are the quality markers the China Pharmacopoeia Commission recognises for Coptis rhizome.
Berberrubine
Protoberberine alkaloidConcentration: Quantified in Coptis rhizome; correlates with the bitter aftertaste measured by electronic tongue
A demethylated berberine that tracks the drug's bitter aftertaste: the higher the aftertaste value, the higher the berberrubine content. It is also a circulating metabolite of berberine, so its presence in the crude drug complicates interpretation of berberine pharmacokinetics.
⚠ Drug Interactions
Cyclosporin A
In a randomised controlled clinical trial, 52 renal transplant recipients took cyclosporin A with berberine 0.2 g three times daily for three months and 52 took cyclosporin A alone. Final cyclosporine trough concentrations and concentration-to-dose ratios were 29.3 and 27.8 percent higher in the berberine group than in controls. A pharmacokinetic substudy in six recipients given berberine for 12 days confirmed increased cyclosporine exposure. No adverse effect on liver or renal function was seen over the trial period. The evidence is for isolated berberine, which is the principal alkaloid of this rhizome; the crude drug has not been studied against cyclosporine directly.
Clinical note: Do not add or withdraw Coptis rhizome in a transplant recipient without cyclosporine level monitoring. Starting the herb can push levels into the toxic range and stopping it can drop them below the therapeutic threshold. The same caution applies to tacrolimus and sirolimus by analogy, although those have not been studied with berberine in transplant patients.
Ceftriaxone, sulfonamides and other bilirubin-displacing drugs
Berberine displaces bilirubin from albumin about ten times more potently on a molar basis than phenylbutazone, itself a known potent displacer. Chronic intraperitoneal berberine in rats lowered mean bilirubin protein binding and raised steady-state unbound and total serum bilirubin. The published work explicitly ties this to reports of kernicterus risk in jaundiced Chinese newborns given berberine-containing herbs. Any co-administered drug that also competes for the same albumin site is expected to add to that displacement.
Clinical note: Do not give Coptis rhizome or berberine-rich formulas to neonates, to jaundiced infants, or to pregnant women near term. Where a neonate is already receiving ceftriaxone or a sulfonamide the combination should be regarded as contraindicated rather than merely cautioned.
CYP2D6 inhibitors including paroxetine, fluoxetine, bupropion and quinidine
A human clinical pharmacology study with genotyped participants showed that CYP2D6 polymorphisms significantly affect berberine metabolism, but only in women: female poor CYP2D6 metabolisers had an 80 percent lower metabolite-to-berberine ratio, and women overall had a 2.8-fold higher AUC and 3.6-fold higher Cmax than men. Berberine is also an OCT1 substrate in vitro, although OCT1 deficiency did not alter its pharmacokinetics in people. Pharmacological CYP2D6 inhibition should therefore mimic the poor-metaboliser phenotype and raise berberine exposure, most markedly in women.
Clinical note: Expect higher berberine exposure when a strong CYP2D6 inhibitor is co-prescribed, and more so in female patients. The clinically important consequence is not berberine toxicity per se but the amplification of berberine's own inhibitory effects on drugs such as cyclosporine.
Huang Lian (Coptidis Rhizoma from Coptis chinensis, Coptis deltoidea or Coptis teeta)
This species is the Japanese and Korean pharmacopoeial Coptis, Oren, and is a recognised source of Coptis Rhizome in those pharmacopoeias. It is not one of the source species the Chinese Pharmacopoeia admits for Huang Lian, which are Coptis chinensis, Coptis deltoidea and Coptis teeta. Quantitative comparison of ten alkaloids across all four species by UHPLC-QQQ-MS/MS separates them, with jatrorrhizine, columbamine and magnoflorine the differentiating compounds, and electronic tongue analysis distinguishes them on taste as well. The drugs are close relatives, not the same material.
Clinical note: Treat Japanese Oren and Chinese Huang Lian as related but not interchangeable, and record which was dispensed. Berberine-based dosing and interaction data transfer reasonably between them; species-specific alkaloid ratios and any activity attributed to the minor alkaloids do not.
Dosage Calculator
⚖ Dosage Calculator
A weight-based mathematical estimate for Coptis japonica. Not a prescription.
Evidence Tier
Moderate 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
0
Randomized controlled trial
1
1 verified · 0 unverified
Other clinical trial
1
1 verified · 0 unverified
Observational / case report
0
In vitro / animal
4
0 verified · 4 unverified
Show 4 studies
- Displacement of Bilirubin from Albumin by Berberine
- Organic cation transporter 1 and cytochrome P450s play crucial roles in coptisine- and worenine-induced hepatotoxicity
- Coptis japonica Makino ethanol extracts attenuates cancer cachexia induced muscle and fat wasting through inhibition of the STAT3 signaling pathway
- Coptis japonica Makino extract suppresses angiogenesis through regulation of cell cycle-related proteins
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
Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study
Randomised controlled trial in 104 renal transplant recipients: 52 received cyclosporin A with berberine 0.2 g three times daily for three months, 52 received cyclosporin A alone. Cyclosporine trough concentrations and concentration-to-dose ratios rose in both arms but ended 29.3 and 27.8 percent higher in the berberine arm, with no detectable effect on liver or renal function. A 12-day pharmacokinetic substudy in six patients confirmed increased cyclosporine exposure. The intervention was isolated berberine rather than Coptis rhizome.
Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans
Genotype-stratified human pharmacokinetic study, registered as NCT05463003, combining in vitro transporter work with dosing in participants selected for OCT1 and CYP2D6 genotype. Berberine was confirmed as an OCT1 substrate in vitro, but OCT1-deficient participants showed no pharmacokinetic difference. CYP2D6 genotype affected berberine metabolism only in women, where poor metabolisers had an 80 percent lower metabolite ratio; women had 2.8-fold higher AUC and 3.6-fold higher Cmax than men. Oral bioavailability was low throughout. The study used berberine, not the crude rhizome.
Displacement of Bilirubin from Albumin by Berberine
Using the peroxidase kinetic method, berberine displaced bilirubin from albumin about ten times more potently on a molar basis than phenylbutazone and about a hundred times more potently than papaverine. Berberine given intraperitoneally to adult rats at 10 and 20 micrograms per gram daily for a week significantly lowered mean bilirubin protein binding and produced a persistent rise in unbound and total serum bilirubin. The paper concludes that huanglian and other berberine-rich traditional medicines are best avoided in jaundiced neonates and in pregnancy. In vitro plus rat work, framed around reported kernicterus risk in newborns.
Organic cation transporter 1 and cytochrome P450s play crucial roles in coptisine- and worenine-induced hepatotoxicity
Coptisine and worenine, isoquinoline alkaloids of Coptidis Rhizoma, caused hepatotoxicity in primary mouse and human hepatocytes and in mice. Both accumulated in liver through OCT1-mediated uptake exceeding MATE1-mediated efflux, and CYP1A2, CYP2D6 and CYP3A4 converted their methylenedioxyphenyl groups into reactive quinone-like metabolites; UGT activity reduced toxicity by limiting reactive metabolite formation. Coptisine was first characterised from Coptis japonica, but the study used isolated alkaloids rather than this species' extract, and worenine is documented mainly from Coptis chinensis.
Coptis japonica Makino ethanol extracts attenuates cancer cachexia induced muscle and fat wasting through inhibition of the STAT3 signaling pathway
Ethanol extract of this species reduced the muscle E3 ubiquitin ligases Atrogin-1 and MuRF1 and raised myosin heavy chain in myotubes exposed to CT26 conditioned medium, and in CT26-bearing mice limited muscle and fat loss while normalising creatine kinase, albumin, triglycerides, cholesterol, HDL and LDL and lowering serum IL-6, apparently through suppression of STAT3 activation. Mouse model; no human cachexia data exist for this herb.
Coptis japonica Makino extract suppresses angiogenesis through regulation of cell cycle-related proteins
Extract of this species inhibited VEGF-stimulated proliferation, migration, invasion and tube formation in human umbilical vein endothelial cells and microvessel sprouting ex vivo, arresting cells in G1 and lowering cyclin D, cyclin E, Cdk2 and Cdk4. Cell and explant work only, with no dosing that can be translated to a patient.
Historical Texts
Shen Nong Ben Cao Jing (Divine Husbandman's Classic of the Materia Medica)
Compiled by the Han dynasty, c. 200 CEShang Han Lun (Treatise on Cold Damage)
Han dynasty, c. 200-220 CEWai Tai Mi Yao (Arcane Essentials from the Imperial Library)
Tang dynasty, 752 CEJapanese Pharmacopoeia, Coptis Rhizome monograph
Modern, current editionsReferences
- Jin Wang, Lin Wang, Guan-Hua Lou, Hai-Rong Zeng, Ju Hu, Qin-Wan Huang, Wei Peng, Xiang-Bo Yang. Coptidis Rhizoma: a comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology . Pharmaceutical Biology (2019) [DOI]
- Yufeng Huang, Wenhui Luo, Wenhan Pei, Dongmei Sun, Hua Zhou, Fan He. Study on the correlation between alkaloids and tastes of Coptis Rhizome from four species based on UHPLC-QQQ-MS/MS combined with electronic tongue technique . Frontiers in Plant Science (2024) [DOI]
- Zenjiro Kitasato. On the Constitution of Coptisine, a New Alkaloid from Coptis Japonica. . Proceedings of the Imperial Academy (1926) [DOI]
- Mihoko Otani, Nobukazu Shitan, Kyoko Sakai, Enrico Martinoia, Fumihiko Sato, Kazufumi Yazaki. Characterization of Vacuolar Transport of the Endogenous Alkaloid Berberine in Coptis japonica . Plant Physiology (2005) [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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