Aim and Objective: 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.
Materials and Methods: Chemical constituents of GSZD and diabetes-related target proteins were
collected from various databases. Then, compounds were filtered by Lipinski’s and Veber’s 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 the 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 the 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.
Results: A total of 275 potential active compounds with 57 possible pathways in GSZD were identified
by 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: These results showed that molecular docking combined with network pharmacology is a
feasible strategy for exploring bioactive compounds and mechanisms of Chinese medicines, and GSZD
can be used to effectively treat diabetes through multi-components and multi-targets & pathways.