THE EFFECTS OF HOUPO EXTRACTIVE ON DRUG METABOLISM ENZYMES OF HUMAN LIVER MICROSOME

Objective To observe the effects of Houpo extractive on five main drug metabolism enzymes(CYP1A2, CYP2C9,CYP2C19,CYP2D6 and CYP3A4)of human liver microsome,and provide theoretical basis for clinical combined use of traditional Chinese medicine and western medicine. Methods Human liver microsome incubation experiment was carried out to assay the extractive on the catalytic activities of the enzymes.Phenacetin,tolbutamide,S-mephenytoin,dextromethorphane and midazolam were used as the substrates of CYP1A2,CYP2C9,CYP2C19,CYP2D6 and CYP3A4,respectively.After incubation, the metabolites of the substrate were quantified by HPLC-MS/MS method.The inhibitions of five main drug metabolism enzymes were calculated by comparing the formation velocities of metabolites with or without Houpo extractive. Results Under 10mg/ L,Houpo had a strong inhibitory effect on the activity of CYP2C9 and CYP2C19,being(94.9±0.38)%and(90.3±0.26)%,respectively,Houpo showed no significant inhibitory effects on the activity of CYP1A2,CYP2D6 and CYP3A4.The IC50 values of CYP2C9 and CYP2C19were 0.470mg/L and 0.717mg/L,respectively,by logarithmic function. Conclusion Houpo extractive has a strong inhibitory effect on the activity of CYP2C9 and CYP2C19,taking it with other drugs should be careful to avoid potential problems such as drug interactions.