Network pharmacology-based investigation of potential targets of astragalus membranaceous-angelica sinensis compound acting on diabetic nephropathy

To explore the mechanism of the Astragalus membranaceous (AM)-Angelica sinensis (AS) compound in the treatment of diabetic nephropathy (DN) we used network pharmacology and molecular docking. Screen the components and targets of the AM-AS compound in the TCMSP and the BATMAN-TCM, and establish a component-target interaction network by Cytoscape 3.7.2. After searching relevant targets of DN in related databases, the common targets of the AM-AS compound and DN were obtained by comparison. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were performed through David database. Molecular docking was performed by PyMoL2.3.0 and AutoDock Vina software. After screening, 142 main targets of the AM-AS compound in the treatment of DN have been identified. Target network was established and the topology of PPI network was analyzed. KEGG pathway enrichment analysis shows that these targets are related to apoptosis, oxidative stress, inflammation, insulin resistance, etc. Molecular docking shows that the target proteins have good combinations with the main active components of the AM-AS compound. AM-AS compound may treat DN by acting on VEGFA, TP53, IL-6, TNF, MARK1, etc., and regulate apoptosis, oxidative stress, inflammation, glucose, and lipid metabolism processes. The in vivo study results suggest that AM-AS compound can significantly reduce the FBG level of diabetic rats, increase the level of INS, improve renal functions, reduce urinary proteins, inhibit glycogen deposition, granulocyte infiltration and collagen fiber proliferation in renal tissue, and restrain the progress of DN. In vivo study combined with network pharmacology and molecular docking methods provides new ideas for the pathogenesis and treatments of DN.