Herbal medicines are widely used worldwide, often alongside prescription drugs, creating the potential for clinically significant herb-drug interactions. These interactions are frequently mediated by effects on drug-metabolizing enzymes (DMEs), particularly those of the cytochrome P450 (CYP450) family, as well as phase II conjugation pathways. This review examines current evidence on how selected herbal extracts influence key enzymes such as cytochrome P450 family 3 subfamily A member 4 (CYP3A4), cytochrome P450 family 2 subfamily D member 6 (CYP2D6), cytochrome P450 family 2 subfamily C member 9 (CYP2C9), and UDP-glucuronosyltransferases (UGTs), and highlights the implications for drug safety and efficacy. Major findings from the literature indicate that herbs like St. John's Wort, Ginkgo biloba, and turmeric can either inhibit or induce enzyme activity, leading to altered drug metabolism. However, results vary widely due to differences in extract composition, dosage, study design, and genetic factors among populations. It is important to note that there remains less clinical evidence as compared to in vitro or animal data, which makes it necessary to be careful when interpreting the results. In addition to pharmacokinetic interactions, this review discusses potential toxicity concerns and safety risks linked to the use of herbal medicinal products. It also outlines key challenges in effectively monitoring and regulating their safe use in clinical practice. Investigating, standardizing herbal product quality, improving study methodologies, and integrating pharmacogenomic data will be essential steps toward ensuring patient safety when combining herbal and conventional therapies.
Keywords: CYP2C9; CYP2D6; Herb–drug interactions; UDP-glucuronosyltransferase; cytochrome P450; drug metabolism; phytochemicals; traditional medicine.