Interactions between cytochrome P450 enzymes and traditional Chinese herbs: A comprehensive review

Cytochrome P450 (CYP) enzymes, predominantly expressed in the liver and intestine, are central to phase I drug metabolism. The CYP1, CYP2, and particularly CYP3 families account for most oxidative biotransformation and nearly half of all drug elimination. Their activities are modulated by genetic polymorphisms, environmental factors, and drug interactions, contributing to interindividual variability in drug efficacy, safety, and susceptibility to drug-induced liver injury. This study systematically evaluated the regulatory effects of commonly used Traditional Chinese Medicine (TCM) and Western herbal medicines on major CYP isoforms. PubMed and Google Scholar were searched for studies published between January 2000 and March 2025, with UpToDate used as a supplementary resource. Eligible evidence included in vitro assays, in vivo animal studies, human pharmacokinetic investigations, and well-documented case reports assessing herbal effects on CYP3A4, CYP2C9, CYP2D6, and CYP1A2. Evidence was graded by strength and integrated with mechanistic and pharmacokinetic data for interaction risk assessment. Herbal candidates included Astragalus membranaceus (Huangqi, ), Salvia miltiorrhiza (Danshen, ), Ginkgo biloba (Ginkgo, ), Bupleurum chinense (Chaihu, ), and Hypericum perforatum (St. John's wort, ). Many herbs demonstrated clinically relevant induction or inhibition of CYP activity, particularly CYP3A4, with the potential to alter drug exposure, reduce therapeutic efficacy, or increase toxicity. Collectively, these findings underscore the imperative for systematic assessment of CYP-mediated herb-drug interactions in integrative medicine and support the development of safer, personalized therapeutic strategies grounded in a refined understanding of metabolic variability.