Inhibitory effects of eleven active components of salvia miltiorrhiza Bge. extract on catalytic activity of cytochrome p450 enzymes in human liver microsomes / 中国药学杂志

ABSTRACT

OBJECTIVE: To predict the potential for drug-drug interactions of Salvia miltiorrhiza Bge. preparations with other-drugs, the effects of 11 active components of Salvia miltiorrhiza Bge. on the catalytic activities of 5 drug-metabolizing enzymes were assessed. METHODS: Human liver microsome incubation experiment was carried out to assay these components on the catalytic activities of these enzymes. Phenacetin, tolbutamide, 5-mephenytoin, dextromethorphane and midazolam were used as the substrates of (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, respectively. After the incubation, the metabolite of each substrate was quantified by LC-MS/MS method. The inhibitions of five main drug metabolism enzymes were calculated by comparing the formation velocities of metabolites with or without Salvia miltiorrhiza Bge. component. RESULTS: Some components of Salvia miltiorrhiza Bge. showed obvious inhibiton on the catalytic activities of CYPs, especially dihydrotanshinone I showed strong inhibiton on CYP3A4 with IC50 value of 0.367 μmol·L-1. CONCLUSION: Salvia miltiorrhiza Bge. preparation with high content of dihydrotanshinone I may cause drug-drug interactions. To predict the interaction precisely, the content of dihydrotanshinone I as well as its in vivo process need a further study.