Yan-Li Wei - Jinhua Polytechnic, Jinhua ۳۲۱۰۰۷, Zhejiang, PR China
Hong-Jian Du - Jinhua Polytechnic, Jinhua ۳۲۱۰۰۷, Zhejiang, PR China
Yi-Ping Lin - Jinhua Polytechnic, Jinhua ۳۲۱۰۰۷, Zhejiang, PR China
Mei-Ling Wu - Jinhua Polytechnic, Jinhua ۳۲۱۰۰۷, Zhejiang, PR China
Ren-ai Xu - The First Affiliated Hospital of Wenzhou Medical University, Wenzhou ۳۲۵۰۰۰, Zhejiang, PR China

Objective(s): In this study, we aimed to evaluate the effect of salidroside on the activities of the different drug-metabolizing enzymes CYP۱A۲, CYP۲B۶, CYP۲C۹, CYP۲D۶ and CYP۳A۴ in rats, in which a specific probe drug was used for each enzyme. Materials and Methods: After pretreatment with salidroside, five probe drugs were simultaneously administered to rats by gavage. The given dose was ۲.۰ mg/kg for phenacetin (CYP۱A۲ activity), ۴.۰ mg/kg for bupropion (CYP۲B۶ activity), ۲.۰ mg/kg for losartan (CYP۲C۹ activity), ۸.۰ mg/kg for metoprolol (CYP۲D۶ activity) and ۱.۰ mg/kg for midazolam (CYP۳A۴ activity). Then, an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the concentrations of rats’ blood, which were collected at different corresponding times. Results: Our data showed that salidroside exhibited an inductive effect on CYP۱A۲, CYP۲B۶, CYP۲C۹ and CYP۳A۴ activities by changing the main pharmacokinetic parameters (t۱/۲, CL/F, Cmax and AUC(۰-∞)) of the four probe drugs in rats. However, no significant changes in CYP۲D۶ activity were observed. Conclusion: In a word, the results displayed that salidroside could induce the activities of CYP۱A۲, CYP۲B۶, CYP۲C۹ and CYP۳A۴, which may influence the disposition of the drugs that are mainly metabolized by these pathways. Our research can provide the basis for the study of related herb-drug interactions in clinic.

Cytochrome P۴۵۰, Cocktail, Enzyme, Herb-drug interaction, Salidroside