Integration of network pharmacology with experimental verification reveals the hypoglycemic mechanism of coptisine in Jinqi Jiangtang tablets: inhibition of the FoxO1 signaling pathway and hepatic gluconeogenesis

Background:Jinqi Jiangtang tablets (JQJT) have been approved for the treatment of type 2 diabetes mellitus (T2DM) in China for many years. Exploring the effective substances and mechanisms of JQJT is important for its clinical application and further drug research and development. This study aimed to explore the chemical basis and mechanisms of JQJT in the treatment of T2DM. Methods: With network pharmacology, we screened substances in JQJT and their possible targets, then constructed the action network and enriched the biological functions and pathways associated with the active components, and identified the potential targets and mechanisms of JQJT in the treatment of T2DM. Based on the network pharmacology data, we explored the hypoglycemic mechanisms of coptisine in JQJT through western blot and quantitative real-time polymerase chain reaction. Results:Forty-three compounds with good pharmacokinetic properties were identified in JQJT, together with 146 potential biological targets. Among these potential targets, 74 were associated with treatment of T2DM. A compound-target network of the 43 compounds against T2DM was constructed. Biological process and signal pathway enrichment analysis of the network highlighted the FoxO signaling pathway. Western blot and quantitative real-time polymerase chain reaction results showed that coptisine, but not epiberberine, significantly inhibited expression of key genes involved in hepatocyte gluconeogenesis by regulating the FoxO1 signaling pathway. Conclusion:Network pharmacology analysis and cell experiments showed that coptisine regulated glucose homeostasis by inhibiting the FoxO1 signaling pathway and hepatic gluconeogenesis, which may be one of the mechanisms of JQJT in the treatment of T2DM.