A mechanism to improve early diabetic nephropathy by modulating autophagy-related mechanisms with Yuye Decotion

Objective: To investigate the molecular mechanisms of Yuye Decotion in the treatment of diabetic kidney disease using network pharmacology methods and molecular docking techniques. Methods: Obtain the transcriptome gene expression of diabetic nephropathy through GEO database, and extract genes related to autophagy. Screen the active ingredients and corresponding targets of Yuye Decoction through the TCMSP database, and map the drug prediction targets and disease targets to obtain the autophagy-related Yuye treatment targets for diabetic nephropathy point. Use String database combined with Cytoscape 3.7.2 software to construct the "drug-active ingredient-target" network and protein interaction network of Yuyetang for the treatment of diabetic nephropathy. The target point of liquid soup in the treatment of diabetic nephropathy was analyzed by GO biological process enrichment analysis and KEGG pathway enrichment analysis, and finally used Pymol and other software to analyze the core active components of Yuye Decotion and The core target protein undergoes molecular docking verification. Results: (i)100 eligible diabetic nephropathy and autophagy related genes were screened, and the potential targets of Yuye Decoction were 1,428. The acquired genes related to diabetic nephropathy and autophagy were mapped to potential targets of Yuye Decoction, and 22 therapeutic targets were obtained. GO biological process enrichment analysis and KEGG pathway enrichment analysis found that the pathways related to autophagy in the treatment of diabetic nephropathy by Yuye Decoction may include mTOR signaling pathway, phospholipase D signaling pathway, insulin resistance, EGFR tyrosine kinase inhibitor resistance, Apoptosis, PI3K /Akt signaling pathway, NF-κB signaling pathway, etc. (ii)The protein interaction network shows that VEGFA, ERBB2, GASP3, MAPK8, MYC, CDKN1A, EGFR, BCL2L1 may be the key targets of Yuye Decoction in the treatment of diabetic nephropathy. Molecular docking realizes the binding of 4 core active ingredients to 8 core target proteins. Conclusions: The research results show that Yuye Decoction treats diabetic nephropathy through multi-component, multi-target, and multi-pathway action, and provides new theoretical basis for the study of pharmacological effects and clinical application of Yuye Decoction in the treatment of diabetic nephropathy in autophagy-related aspects.