Molecular mechanism of Yi-Qi-Yang-Yin-Ye against obesity in rats using network pharmacology, molecular docking, and molecular dynamics simulations

The increasing prevalence of obesity globally, which as well as affecting people's daily lives and increasing the risk of obesity complications, also threatens the health of animal organisms simultaneously. It's been reported that Yi-Qi-Yang-Yin-Ye had remarkable efficacy in the treatment of obesity. The specific underlying mechanism of action of Yi-Qi-Yang-Yin-Ye in treating obesity, however, remains ambiguous. Therefore, the innovative approach, which is network pharmacology combined with molecular docking and molecular dynamics simulations, was employed in the current research to explore the potential mechanism and promote further development in the treatment of obesity. The active ingredients and related targets of Yi-Qi-Yang-Yin-Ye and related targets of obesity were summarized from extensive public databases. Furthermore, network topology analysis and pathway enrichment analysis were performed to explore the complicated interactions between drug and targets. Finally, accurate validation methods composed of molecular docking and molecular dynamics simulations were conducted to elucidate the binding affinity of Yi-Qi-Yang-Yin-Ye with obesity-related targets. As a result, 13 main active ingredients and 5 core targets of Yi-Qi-Yang-Yin-Ye against obesity in rats were acquired through primary screening of network topology analysis. Pathway enrichment analysis demonstrated that intersectional targets were involved in multiple signaling pathways, where PI3K-Akt signaling pathway, MAPK signaling pathway, and Insulin resistance were the main pathways of Yi-Qi-Yang-Yin-Ye in treating obesity in rats. Finally, molecular docking indicated that the seven critical active ingredients displayed great binding affinity to the hub targets. Furthermore, molecular dynamics simulations further screened and obtained that five critical active ingredients acting on the Mapk1 target for Yi-Qi-Yang-Yin-Ye against obesity in rats. The innovative approach and the results achieved have further contributed to and revealed the molecular mechanisms for treating obesity, providing an alternative for treating obesity in animals and humans.