Evaluation of the Inhibition of Cytochrome P450 Activity by Ginsenoside Rg5 and Rk1

Background: Heat-treated red ginseng contains pharmacologically active ginsenosides such as Rg5 and Rk1 and is increasingly used as a functional food. Because herbal products are frequently co-administered with conventional medications, evaluation of potential cytochrome P450 (CYP)-mediated drug–drug interactions is essential. This study examines their effects on nine cytochrome P450 isoforms to evaluate potential drug–drug interactions. Methods: The CYP enzyme inhibition method was assessed by determining IC50 values using human liver microsomes and specific substrates. Various concentrations of ginsenosides Rg5 and Rk1 were tested, and the reactions were analyzed via UPLC-MS/MS. Positive control inhibitors were included for comparison. Results: Ginsenoside Rg5 and Rk1 exhibited potent inhibitory effects on CYP2A6, with IC50 values of 1.04 and 0.98 μM, respectively, with moderate inhibitory effects observed for several other CYP activities and little or no inhibition observed for the remaining CYP activities. Conclusions: The results indicate potential adverse drug reactions with CYP2A6-metabolized drugs, highlighting the need for further in vivo safety evaluations. These findings provide important information regarding CYP-mediated herb–drug interaction potential associated with heat-processed ginsenosides.