The effects of Glycyrrhizae uralenis and its major bioactive components on pharmacokinetics of daphnetin in Cortex daphnes in rats

Glycyrrhizae uralenis (GU) is often prescribed together with Cortex daphnes (CD) in traditional Chinese medicinal practice to increase the efficacy of CD on the treatment of rheumatoid arthritis (RA), but the reasons were still unknown. In order to clarify the rationality of herbaceous compatibility between CD and GU, the comparative evaluations on pharmacokinetic behaviors of daphnetin (a predominantly active ingredient in CD) after intragastric administration of CD and CD–GU (combination of CD and GU) extract were studied. In addition, the effects of glycyrrhizin and liquiritin, active ingredients of Glycyrrhiza triterpenes and Glycyrrhiza flavones respectively, on the pharmacokinetics of daphnetin were also investigated. Five groups of rats were orally administered with CD extract, CD–GU extract, pure daphnetin, co-administration of daphnetin and glycyrrhizin as well as co-administration of daphnetin and liquiritin at the same single dose of daphnetin (20mg/kg). The rat plasma concentrations of daphnetin were determined by our developed UPLC–MS/MS method. The pharmacokinetics of daphnetin in above groups were investigated and compared. Comparing with oral administration of CD extract, AUC and Tmax of daphnetin significantly increased after giving CD–GU (p