A Study on the Mechanism of Milkvetch Root in the treatment of Diabetic Nephropathy based on Network Pharmacology

Abstract Background: Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. Milkvetch Root has been extensively used to treat DN in clinical practice in China for many years, but the active ingredients, drug targets, and its exact molecular mechanism are not known. The aim of this study was to decrypt the underlying mechanisms of Milkvetch Root in the treatment of DN by using a systems pharmacology approach. Methods: The components and targets of Milkvetch Root were analyzed using the Traditional Chinese Medicine Systems Pharmacology database. Then we found the common target of Milkvetch Root and disease, constructed a protein-protein interaction (PPI) network using String, and screened the key targets from these common targets through topological analysis. Analyses of enrichment of Gene Ontology (GO) pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Subsequently, the major hubs were imported to the Database for Annotation, Visualization and Integrated Discovery to perform a pathway enrichment analysis. Results: There were 20 active compounds of Milkvetch Root and 10 diabetic nephropathy -associated targets (AKT1, VEGFA, IL6, PPARG, CCL2, NOS3, SERPINE1, CRP, ICAM1, SLC2A4) that were obtained. Then, the results of GO and KEGG pathway enrichment analyses suggested that the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, PI3K-Akt signaling pathway and TNF signaling pathway in diabetic complications might serve as the key points and principal pathways for DN treatment. Conclusions: In brief, Milkvetch Root has multiple components, multiple targets and multiple pharmacological effects in the treatment of DN, which provides clues for further research on DN.