In vitro evaluation of the effects of traditional herbal formulas on human Cytochrome P450 isozymes

Abstract

The aim of this study was to assess influence of Sagunja‐tang (SGT; Sizunji‐tang, Shikunshi‐to), Samul‐tang (SMT; Siwu‐tang, Shimotsu‐to), Palmul‐tang (PMT; Bawu‐tang) and Sipjeondaebo‐tang (SJT; Shiquandabu‐tang, Juzentaiho‐to) on the activities of human cytochrome P450 (CYP450), a drug‐metabolizing enzyme. These popular herbal formulas have been used in Asian countries for the prevention and treatment of various diseases. Herbal formulas usually consist of mixtures of crud drugs, and the chance of herb–drug interactions may increase when they are coadministered with conventional drugs. In this study, we established in vitro fluorescence‐based enzyme assays for major human CYP450 isozymes (CYP3A4, CYP2C19, CYP2D6 and CYP2E1) using Vivid® CYP450 Screening Kits. Among these four CYP450 isozymes, CYP2C19 was inhibited by all the tested herbal formulas. In contrast, SGT, SMT and SJT inhibited CYP2E1‐mediated metabolism; and PMT exhibited comparatively weak inhibition of CYP2E1. However, none of the four herbal formulas significantly affected CYP3A4 or CYP2D6. These results suggest that SGT, SMT, PMT and SJT could potentially inhibit the metabolism of coadministered drugs of which primary route of elimination is via CYP2C19. In addition, clinically relevant pharmacokinetic interactions could occur when SGT, SMT or SJT is coadministered with drugs metabolized by CYP2E1. Overall, our findings provide information for the safe and effective clinical use of these four herbal formulas.