Effects of Tokishakuyakusan, Keishibukuryogan, and Kamishoyosan on the expression and activity of drug-metabolizing enzymes in the liver and small intestine

Abstract

The mechanisms of action of traditional herbal medicines are being actively researched, but little information is available regarding the interactions of these agents with concomitant drugs; clarifying these interactions is extremely important for the appropriate and safe use of these agents. Changes in the expression of drug-metabolizing enzymes are essential for determining drug-drug interactions. In this study, we investigated the effects of traditional herbal medicine on the expression and activity of cytochrome P450 (Cyp), a drug-metabolizing enzyme. This study focused on Tokishakuyakusan (TSS), Keishibukuryogan (KBG), and Kamishoyosan (KSS), which are effective for treating symptoms unique to women. Female mice were given normal chow or chow containing TSS, KBG, or KSS for four weeks. The mRNA levels of Cyp in the liver and small intestine were analyzed, and the Cyp3a protein level and metabolic activity were also evaluated. No significant differences in the mRNA expression levels of Cyp isozymes in the liver and small intestine were detected between the TSS-treated group and the control group. The protein expression level and metabolic activity of Cyp3a, which is the most important enzyme for drug metabolism, were not affected by TSS administration. In addition, no changes in the expression level and metabolic activity of Cyp in the liver and small intestine were detected in mice who were fed KBG or KSS. The results of this study revealed that TSS, KBG, and KSS do not affect Cyp expression and activity. Therefore, these herbal medicines are unlikely to interact with Cyp substrate drugs.