Network Pharmacology and Molecular Docking Analysis of Zisheng Decoction for Diabetic Gastroparesis: Mechanism Exploration

Abstract

Objective: The primary goal of the current research was to investigate the bioactive constituents, candidate therapeutic targets, and underlying therapeutic mechanisms of Zisheng Decoction (ZSD) in the treatment of diabetic gastroparesis (DGP). This was achieved by applying a combined approach of network pharmacology and molecular docking simulations. Methods: Information regarding the bioactive compounds of ZSD and their corresponding targets was mined from multiple pharmacological databases. Simultaneously, gene targets associated with DGP were obtained utilizing the OMIM and GeneCards datasets. We constructed a protein-protein interaction (PPI) network to analyze intersecting targets and utilized Cytoscape to screen for hub genes. Furthermore, functional roles and involved signaling routes were mapped via enrichment analysis of GO and KEGG. Finally, the interactive potential between the primary constituent compounds and their primary targets was validated using molecular docking techniques. Results: A total of 46 active compounds and 593 predicted targets related to Zisheng Decoction (ZSD) were identified, along with 252 targets associated with diabetic gastroparesis (DGP). Then, we intersected 46 bioactive compounds, 593 putative targets, and 252 disease-associated targets to obtain 13 shared targets, of which GCK, PPARG, INSR, AKR1B1 and PDGFRA were considered to be potential key therapeutic targets based on degree centrality and functional relevance. Gene Ontology (GO) enrichment analysis indicated that most targets were significantly associated with biological processes involving glucose balance and insulin secretion. KEGG pathway analysis revealed a primary concentration in the AMPK signaling pathway, type 2 diabetes mellitus, galactose metabolism, and longevity regulation pathways. Furthermore, molecular docking simulations demonstrated that certain active ingredients in ZSD could bind stably and with high affinity to the core targets GCK and PPARG with high affinity. Conclusion: Zisheng Decoction (ZSD) has therapeutic effects on diabetic gastroparesis (DGP) via a mechanism involving multiple targets and pathways, including modulating glucose metabolism, restoring gut motility and mucosal health, ameliorating insulin resistance, and reducing chronic low-grade inflammation. Such results provide a scientific basis for ZSD's clinical application in DGP therapy.