Identification of the active constituents and significant pathways of Guizhi-Shaoyao-Zhimu Decoction for treatment of diabetes mellitus based on molecular docking and network pharmacology.

This study was designed to explore the active compounds and significant pathways of Guizhi-Shaoyao-Zhimu decoction (GSZD) for treating diabetes mellitus using molecular docking combined with network pharmacology.Chemical compnents of GSZD and diabetes-related target proteins were collected from various databases. Then, compounds were filtered by Lipinski' and Veber' rules with Discovery studio software. The "Libdock" module was used to carry out molecular docking, and LibDockScores, default cutoff values for hydrogen bonds, and van der Waals interactions were recorded. LibDockScore of target protein and its prototype ligand was considered as the threshold, and compounds with higher LibDockScores than the threshold were regarded as the active constituents of GSZD. Cytoscape software was used to construct herb-active molecule-target interaction network of GSZD. ClueGO and CluePedia were applied to enrich the analysis of the biological functions and pathways of GSZD.A total of 275 potential active compounds with 57 possible pathways in GSZD were identified via molecular docking combined with network pharmacology. TEN, INSR, PRKAA2, and GSK3B are the four most important target proteins. Gancaonin E, 3'-(γ,γ-dimethylallyl)-kievitone, aurantiamide, curcumin and 14-O-cinnamoylneoline, could interact with more than 14 of the selected target proteins. Besides, 57 potential pathways of GSZD were identified, such as insulin signaling pathway, metabolites and energy regulation, glucose metabolic process regulation, and positive regulation of carbohydrate metabolic process, etc. Conclusion: Our results showed molecular docking combined with network pharmacology is a feasible strategy for exploring bioactive compounds and mechanisms of Chinese medicines, and GSZD treat diabetes through multi-components and multi-targets & pathways.