Effects of glycyrrhizin on the pharmacokinetics of asiatic acid in rats and its potential mechanism

摘要

>Context: Asiatic acid has been reported to possess a wide range of pharmacological activities.>Objective: This study investigates the effects of glycyrrhizin on the pharmacokinetics of asiatic acid in rats and its potential mechanism.>Materials and methods: The pharmacokinetics of orally administered asiatic acid (20 mg/kg) with or without glycyrrhizin pretreatment (100 mg/kg/day for seven days) were investigated using a LC–MS method. Additionally, the Caco-2 cell transwell model and rat liver microsome incubation systems were used to investigate the potential mechanism of glycyrrhizin’s effects on the pharmacokinetics of asiatic acid.>Results: The results showed that the Cmax (221.33 ± 21.06 vs. 324.67 ± 28.64 ng/mL), AUC0–inf (496.12 ± 109.31 vs. 749.15 ± 163.95 μg·h/L) and the t1/2 (1.21 ± 0.27 vs. 2.04 ± 0.32 h) of asiatic acid decreased significantly (p < 0.05) with the pretreatment of glycyrrhizin. The oral clearance of asiatic acid increased significantly from 27.59 ± 5.34 to 41.57 ± 9.19 L/h/kg (p < 0.05). The Caco-2 cell transwell experiments indicated that glycyrrhizin could increase the efflux ratio of asiatic acid from 1.63 to 2.74, and the rat liver microsome incubation experiments showed that glycyrrhizin could increase the intrinsic clearance rate of asiatic acid from 138.32 ± 11.20 to 221.76 ± 16.85 μL/min/mg protein.>Discussion and conclusions: In conclusion, these results indicated that glycyrrhizin could decrease the system exposure of asiatic acid, possibly by inducing the activity of P-gp or CYP450 enzyme.