Utilizing Network Pharmacology and Molecular Docking to Analyze the Mechanism of Huanglian-Zhimu-Chishao in Treating Type 2 Diabetes Mellitus

This study probed into the therapeutic mechanism of Huanglian-Zhimu-Chishao compound on T2DM via network pharmacology and molecular docking. The major constituents and targets of Huanglian-Zhimu-Chishao were identified by using TCMSP, PubChem and SwissTargetPrediction database. GeneCards and OMIM databases were used to obtain the T2DM-related target genes, the duplicate ones were deleted. We use Venny 2.1.0 to determine the overlap of component and disease target, and then establish a “drug-component-target” network using Cytoscape 3.7.1 to find key active components. String database is used for PPI network analysis, topological screening in Cytoscape is applied for drug-disease targets identification. DAVID database was used to conduct GO and KEGG pathway analysis. Lastly, molecular docking through Autodock and PyMOL were used to examine the binding affinities of the major components and their respective target. A total of 458 targets for Huanglian-Zhimu-Chishao and 2,393 targets for T2DM, 239 targets overlapped. The main active components included quercetin, kaempferol, albiflorin, stigmasterol, and obacunone, and the main targets included AKT1, TNF, IL6, TP53, and EGFR. GO analysis showed that there were 991 BP, 116 CC, and 204 MF. KEGG pathway analysis, 188 pathways. From the results of the molecular docking analysis, we find that there are strong binding affinities between the main targets like AKT1, TNF, IL6, TP53, and EGFR, and the main active ingredients such as quercetin, Kaempferol, Albiflorin, Stigmasterol, and Obacunone. Huanglian-Zhimu-Chishao combination has a multi-target comprehensive effect in T2DM treatment. The active components regulate various disease-related targets through multiple pathways, thereby improving the therapeutic outcome for T2DM.