Trial reportEuropean journal of clinical pharmacology2012
Repeated administration of berberine inhibits cytochromes P450 in humans.
Trial report in European journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Efficacy of Berberine Alone and in Combination for the Treatment of Hyperlipidemia: A Systematic Review.Journal of evidence-based complementary & alternative medicine · 2017Pooled it
- Assessing Transporter-Mediated Natural Product-Drug Interactions Via In vitro-In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail.Clinical pharmacology and therapeutics · 2021Trial
- Berberine as a Promising Antifungal Agent: Insights into Molecular Mechanisms and Therapeutic Potential.ACS omega · 2026Review
- Berberine and its derivatives as candidate modulators of immunosenescence: a critical evaluation.Biogerontology · 2026Review
- Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Metabolic and Anti-Inflammatory Effects of Berberine-Rationale for Its Therapeutic Potential in Polycystic Ovary Syndrome.International journal of molecular sciences · 2026Review
- Bioactive Natural Compounds: A Review of Their Integration into Bone Tissue Engineering Scaffolds.Annals of biomedical engineering · 2026Review
- Obesity and Natural Products: Mechanisms, Therapeutic Potential, and Future Directions.Food science & nutrition · 2026Review
- Coptidis Rhizoma Alkaloids Alleviate Acetaminophen-Induced Liver Injury by Regulating GSH Metabolism and the TNF Signaling Pathway.Antioxidants (Basel, Switzerland) · 2026Article
- Mechanisms and applications of natural plant ingredients in modulating amino acid metabolism for the improvement of diabetic retinopathy: a review.Frontiers in endocrinology · 2026Review
- Berberine as a multitarget modulator of metabolic inflammation: molecular mechanisms, circadian regulation, and translational perspectives.Frontiers in pharmacology · 2026Review
- Gut microbiota-liver-kidney axis in diabetic kidney disease: mechanistic insights into amino acid metabolism and nutritional intervention strategies targeting natural bioactive compounds.Frontiers in nutrition · 2026Review
- The treatment of selected traditional Chinese medicine prescriptions and their metabolites for heart failure with preserved ejection fraction from basic science discovery to the clinic.Frontiers in pharmacology · 2026Review
- From Mechanistic Evidence to Clinical Translation: A Narrative Review of Chinese Herbal Medicine for Insomnia.Drug design, development and therapy · 2026Review
- Medical nutrition therapy for the management of type 2 diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- Berberine's impact on health: Comprehensive biological, pharmacological, and nutritional perspectives.Metabolism open · 2025Review
- ArcDFI: Attention regularization guided by CYP450 interactions for predicting drug-food interactions.PLoS computational biology · 2025Article
- Traditional Chinese medicine compounds modulate signaling pathways to improve cardiac-related pathology.Frontiers in pharmacology · 2025Review
- Effects of Berberis vulgaris, and its active constituent berberine on cytochrome P450: a review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- In silico evaluation of berberine and silymarin against metabolic targets: a rationale for OMICS technology-based co-formulation.In silico pharmacology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeBerberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interactions between berberine-containing products and cytochromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
methodsA two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
resultsA decrease in CYP2D6 activity was observed as the 0-8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the C(max), AUC(0-∞), and AUC(0-12) of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after BBR treatment, respectively. Compared with the placebo period, the T(max) and T(1/2) of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P < 0.05); and the phenotypic indices of 1 h midazolam/1'-hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
conclusionsRepeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.