Evaluation of the effects of NS, SF and CNS on the activities of cytochrome P450 enzymes using a cocktail method in rats.

Abstract

Notoginseng total saponins (NS), safflower total flavonoids (SF) and the combination of NS and SF, namely CNS are used for the treatment of cardiovascular disease (CD) in clinic. In the study, a cocktail assay involving seven cytochrome P450 (CYP) enzymes was performed to elucidate the effect of NS, SF and CNS on CYP enzymes and to explore the synergistic effect of CNS in terms of CYP enzymes. UPLC/MS and RT-PCR were applied to detect the activities and mRNA expression levels of CYP enzymes. SF had the inhibitory effects on CYP1A2, 2B1, 2E1, 2C11 and induction effects on CYP2C19 and 2D4. NS had the induction effects on CYP1A2, 2B1, 2E1, 2C11, 2C19 and 2D4. CNS had the induction effects on CYP1A2, 2B1, 2E1, 2C19, 2D4 and inhibitory effects on CYP3A1 in vivo. Moreover, mRNA expression results had the consistent results with pharmacokinetics. The potential herb-drug interactions (HDI) should be paid close attention when SF, NS or CNS with clinical drugs metabolized by CYP1A2, 2B1, 2E1, 2C11, 2C19, 2D4 and 3A1. CNS could change the inhibition or induction effects of CYP compared to NS group, which might be one of the causes for synergistic effects of combination of NS and SF.