Comparative drug-drug interactions of berberine and astragaloside IV in normal and type 2 diabetes mellitus rats based on UPLC-QqQ-MS/MS

The UPLC-QqQ-MS/MS method was established, validated, and used for the simultaneous detection of berberine (BBR), astragaloside IV (AST), and the main metabolites to demonstrate the comparative pharmacokinetics of BBR and AST in normal and T2DM rats. BBR and AST had reduced the internal exposure of each other and their main metabolites in normal rats. However, AST had few significant effects on the pharmacokinetic parameters of BBR and the main metabolites in T2DM rats. Similarly, BBR had no significant effect on the pharmacokinetic parameters of AST but significantly increased the exposure to cycloastragenol (CAG) in vivo . Molecular docking of BBR and AST with the P-glycoprotein (P-gp) was performed, which indicated that both BBR and AST are potential substrates for P-gp. The differences in gut microbiota between normal and T2DM rats were compared by 16S rRNA sequencing. Git microbiota that could produce β-glucosidase and β-xylosidase were highly abundant in T2DM rats. The current study indicated that BBR and AST had reduced oral bioavailability. The gut microbiota was enriched in the intestines of T2DM rats and promoted the hydrolysis of AST to produce CAG, while the drug-drug interaction between AST and BBR was blocked.