In a groundbreaking study published in the journal Acta materia Medica, researchers have unveiled new insights into the pharmacokinetics of berberine (BBR) and astragaloside IV (AST) in both healthy and type 2 diabetes mellitus (T2DM) rats. The study employed a highly elegant UPLC-QqQ-MS/MS method, which was meticulously developed and validated to together detect these compounds and their primary metabolites.
The findings revealed intriguing differences in how BBR and AST interact within the body. In healthy rats, the presence of each compound reduced the internal exposure of the other, along with their main metabolites. However, in T2DM rats, the dynamics shifted. AST showed minimal impact on BBR’s pharmacokinetics, while BBR, though not affecting AST significantly, notably increased the presence of cycloastragenol (CAG) in the bloodstream.
To delve deeper into these interactions, the researchers conducted molecular docking studies, focusing on P-glycoprotein (P-gp), a key protein involved in drug transport.The results suggested that both BBR and AST could potentially serve as substrates for P-gp, shedding light on their metabolic pathways.
The study also explored the role of gut microbiota, using 16S rRNA sequencing to compare differences between healthy and T2DM rats. Interestingly, T2DM rats exhibited a higher abundance of gut bacteria capable of producing β-glucosidase and β-xylosidase, enzymes that play a crucial role in the hydrolysis of AST into CAG. This enzymatic activity, combined with the altered gut surroundings in T2DM rats, appeared to block the drug-drug interaction between BBR and AST.
the research highlights the complex interplay between these compounds, gut microbiota, and metabolic conditions. It underscores the reduced oral bioavailability of BBR and AST while providing valuable insights into how T2DM influences their pharmacokinetics. As the authors noted, “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.”
source:
Lei, Y. et al. (2025) Comparative drug-drug interactions of berberine and astragaloside IV in normal and type 2 diabetes mellitus rats based on UPLC-QqQ-MS/MS. Acta Materia Medica. doi.org/10.15212/AMM-2024-0078
