Evaluation of regulation of Salvia miltiorrhiza and Panax ginseng on rat liver CYP450 using multiple reaction monitoring / 中草药

ABSTRACT

Objective: To establish a new specific and high-throughput method for CYP450 quantification, and to investigate the effect of drugs on rat liver CYP450 using Salvia miltiorrhiza and Panax ginseng as tool drugs. Methods: Mass spectrometry with multiple reaction monitoring (MRM) was applied to quantify nine rat liver enzyme CYP450 isoforms from the rat model with S. miltiorrhiza and P. ginseng. With QconCAT heavy peptides as internal standard, we aimed to assess the effects of S. miltiorrhiza and P. ginseng on CYP450 isoforms. Results: The relative standard deviation and relative error of this method were less than 5.9% and 6.8%, respectively, with good linearity (r2>0.9). Nine CYP450s isoforms (CYP1A1, CYP1A2, CYP2B1, CYP2B2, CYP2C6, CYP2C11, CYP3A1, CYP3A2, and CYP17A1) in rat liver microsome treated with S. miltiorrhiza and P. ginseng were also quantified. Compared with the control, S. miltiorrhiza downregulated the expression levels of CYP1A1, CYP2B2, CYP3A2, CYP2C11, and CYP17A1, while upregulated CYP1A2 and CYP2B1. For the effects of P. ginseng, the expression of CYP1A1 and CYP2B2 was decreased, while CYP1A2, CYP2B1, CYP3A2, CYP2C11, and CYP17A1 were increased. Conclusion: We successfully construct a method with MRM to quantify rat liver CYP450 isoforms. And we firstly quantify CYP2B1, CYP2B2, and CYP17A1 in rat liver. The results reveal the regulation of CYP450 by S. miltiorrhiza and P. ginseng, which could provide clinical application for drug compatibility in practice, and avoid adverse drug reactions.