Radix Bupleuri-Radix Paeoniae Alba couplet medicine in the treatment of type 2 diabetes mellitus- A network pharmacology and cellular experimental assessment

Introduction: The increasing global incidence of type 2 diabetes mellitus(T2DM) requires new drug interventions. For more than two thousand years, the combination of Radix Bupleuri and Radix Paeoniae Alba couplet medicine (BPCM) has provided beneficial activities in the treatment of diabetes. The object of this network pharmacology study was explore their combined mechanisms with verification In vitro.Methods: The chemical compounds and potential targets of BPCM were analyzed through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene information related to T2DM was collected using GeneCards and OMIM database. The core targets were obtained through Venn Diagram, and the protein interaction network (PPI) was constructed using the STRING database. The networks of compound-target and drug-compound-common target-disease were constructed by Cytoscape. Gene ontology (GO) term enrichment analysis and biological pathway (KEGG) enrichment analysis were performed using R language. SYBYL docking for key compounds with targets were performed to explore their binding modes, which was further verified through cell experiments.Results: The study identified 17 active ingredients in Radix Bupleuri and 13 active ingredients in Radix Paeoniae Alba. There were 23 targets related to type 2 diabetes, including caspase 3 (CASP3), peroxisome proliferation-activated receptor gamma (PPARG) and intercellular adhesion molecule-1 (ICAM1). Further analysis identified 403 GO biological processes and 76 related signal pathways. It was found that CASP3-kaempferol, CASP3-quercetin, and ICAM1-stigmasterol had high binding activities. In the palmitic acid-induced HepG2 cells, BPCM improved lipid aggregation and up-regulated the levels of p-ACC and p-AMPK. Importantly, experimental verification results showed that BPCM increased the expression of PPARG and decreased the levels of CASP3 and ICAM1.Conclusions: Through network pharmacology, molecular docking and vitro experiments, the study found that BPCM may treat T2DM by promoting AMPK/ACC conduction and inhibiting lipid accumulation.

Automated summary

In this study, we used network pharmacology, molecular docking, and in vitro experiments to investigate the mechanism of BPCM in treating T2DM. The results showed that BPCM may promote AMPK/ACC conduction and inhibit lipid accumulation.