The Molecular Mechanisms of Panax ginseng in Treating Type 2 Diabetes Mellitus: Network Pharmacology Analysis and Molecular Docking Validation

Abstract

Background. Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with a high global incidence. Panax ginseng has been used to treat T2DM in traditional medicine, with previous in vitro, in vivo, and clinical trial studies demonstrating its efficacy. This study aimed to determine the mechanism of P. ginseng in treating T2DM by network pharmacology. Methods. The bioactive compounds of P. ginseng and corresponding targets of P. ginseng-T2DM were retrieved across multiple databases. The protein-protein interaction network was established using the STRING database and topological analysis helped identify the core target. Using the DAVID tool, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, we checked the binding of core targets and bioactive compounds using molecular docking. Results. The P. ginseng-T2DM networks mainly contained 22 bioactive compounds and 314 overlapping targets. The five most significant core targets were SRC, STAT3, MAPK1, AKT1, and PIK3R1. There were 244 GO terms and 95 KEGG pathways (adjusted $p<0.01$ ) that were strongly correlated with diabetes-related signaling pathways, such as insulin resistance, the HIF-1 signaling pathway, the PI3K/Akt signaling pathway, the prolactin signaling pathway, the Rap1 signaling pathway, the Ras signaling pathway, the calcium signaling pathway, and the FoxO signaling pathway. Molecular docking results revealed that the top five core targets had a high binding affinity with the bioactive compounds of P. ginseng. Conclusion. The bioactive compounds and targets in P. ginseng ameliorate T2DM by regulating insulin resistance and multiple signaling pathways.