1.The aim of this study was to investigate the effects of glycyrrhizin on the pharmacokinetics of celastrol in rats.2.Twelve male Sprague-Dawley rats were randomly assigned to two groups: control group and test group. Test group was pretreated with glycyrrhizin at a dose of 100mg/kg/day for 10 days, and then the two groups were orally administered with celastrol at a dose of 1mg/kg. The concentration of celastrol was determined using a sensitive and reliable LC-MS method.3.The results showed that glycyrrhizin could significantly decrease the plasma concentration (from 64.36ng/mL to 38.42ng/mL) and AUC(0-t) (from 705.39 to 403.43gh/L) of celastrol in rats. To investigate its potential mechanism, the effects of glycyrrhizin on the transport and metabolic stability of celastrol were investigated using Caco-2 cell monolayer transwell model and rat liver microsome incubation systems. The Caco-2 cell monolayer transwell experiments indicated that glycyrrhizin could increase the efflux ratio of celastrol (4.02 versus 6.51). However, the rat liver microsome incubation experiments showed that glycyrrhizin could significantly increase the intrinsic clearance rate of celastrol from 20.33.37 to 38.8 +/- 4.18L/min/mg protein.4.In conclusion, these results indicated that the herb-drug interaction between glycyrrhizin and celastrol might occur when they were coadministered.