Abstract
Background and Objectives：Chuanxiong Rhizoma is a traditional Chinese herbal medicine. Ferulic acid and senkyunolide A are active compounds of Chuanxiong Rhizoma. The possibility of a drug-drug interaction mediated by cytochrome P450 resulting from ferulic acid and senkyunolide A has not been investigated.This study aims to explore the effects of ferulic acid and senkyunolide A on CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2 activities in rats both in vitro and in vivo.
Methods: In the in vivo study, rats were administered probe drugs of the four isoforms including caffeine, tolbutamide, metoprolol, and dapsone. Blood samples were collected at setting times and determined by ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). In the in vitrostudy, probe drugs phenacetin, tolbutamide, dextromethorphan, and testosterone were used for incubation with rat liver microsomes, and their metabolites were determined by high-performance liquid chromatography (HPLC).
Results: In the in vivo study, both ferulic acid and Senkyunolide A accelerated the metabolism of dapsone but had no significant effect on other probe drugs. In the rat liver microsome incubation system in vitro, the concentrations of 6β-hydroxytestosterone in the ferulic acid-treated group and senkyunolide A-treated group were higher than those in the control group respectively, but the concentrations of other metabolites were not significantly changed.
Discussion and conclusions: Both the in vivo and in vitro results demonstrated that ferulic acid and senkyunolide A can increase the activity of CYP3A1/2, but do not significantly affect the activities of CYP1A2, CYP2C11, and CYP2D1 in rats. This suggests that traditional Chinese medicine containing ferulic acid and senkyunolide A may decrease the curative effects of the drugs metabolized by CYP3A4 in humans.