Network pharmacology-based approach to investigate the mechanism of Huang-Lian-Jie-Du-Decoction for treatment of type 2 diabetes mellitus

Abstract

Background: Although the benefits of Huang-Lian-Jie-Du-Decoction (HLJDD) on type 2 diabetes mellitus are noted, the material base and action mechanism remain unknown. This paper aim is to reveal the material base and action mechanism of HLJDD against type 2 diabetes mellitus in a system pharmacology framework. Methods: The compounds in HLJDD were first retrieved from the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. Once retrieved, they were fed into the SwissTargetPrediction database to predict the interacting targets. Meanwhile, a human expression profile dataset was analyzed in the Gene Expression Omnibus database, and subsequently, the differentially expressed genes were compared to the HLJDD-related targets. We conducted a protein-protein interaction analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and Gene Ontology analysis to identify the potential active compounds and targets. Lastly, to verify the binding affinities of those compounds and targets, we performed molecular docking. Results: We obtained 15 key compounds, such as quercetin, epiberberine, and berberine, and 10 hub genes, such as IκB kinase-β and phosphatidylinositol 3-kinase regulatory subunit alpha. The top 10 enriched pathways were also found to be tightly related to type 2 diabetes mellitus, including insulin resistance and FoxO signaling pathway. Moreover, all the key compounds were found to bind well to the hub genes. Particularly for the target of IκB kinase-β, 11 out of 15 compounds bound to it with energies of