Insights Into the Functional Mechanism of Diabetic Kidney Disease Treatment with Sinensetin Based on Network Pharmacology and Molecular Docking

Abstract

Objective: Sinensetin is an antioxidant widely used for treating various diseases; however, its function and targets in diabetic kidney disease (DKD) remain unknown. This study aimed to investigate the functional mechanism of sinensetin in DKD using network pharmacological and molecular docking methods. Methods: Potential targets of sinensetin for DKD treatment were identified using the Swiss Target Prediction (http://www.swisstargetprediction.ch/), STITCH (http://stitch.embl.de/), Online Mendelian Inheritance in Man (OMIM, https://omim.org/), and GeneCards (https://www.genecards.org/) databases. These potential targets were introduced into the STRING database to analyze protein–protein interactions (PPI) and identify key targets. These key targets were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The binding activities of these key targets were confirmed using molecular docking analysis. Results: A total of 53 key targets of sinensetin treatment in DKD were identified. Ten core targets, including protein kinase SRC (SRC), epidermal growth factor receptor (EGFR), and prostaglandin-endoperoxide synthase 2 (PTGS2) were identified using PPI network interactions. GO functional analysis revealed that reactive oxygen species metabolic processes, membrane rafts, and protein tyrosine kinase activity were involved in sinensetin treatment of DKD. The KEGG enrichment analysis exhibited that signaling pathways such as pathways in cancer, tryptophan metabolism, and the vascular endothelial growth factor (VEGF) signaling pathway play important roles. Molecular docking analysis suggested favorable docking between the ten core targets and sinensetin. Conclusion: Sinensetin plays a role in the treatment of DKD through various biological processes and signaling pathways. These data provide theoretical evidence for experimental studies on DKD treatment using sinensetin.