Unraveling the therapeutic mechanism of Xiezhuo Yishen Decoction in uric acid nephropathy: Active compounds, key targets, and pathway regulation via network pharmacology and molecular docking

This study investigates the potential mechanism of Xiezhuo Yishen Decoction (XYD) in the treatment of uric acid nephropathy (UAN). The active components and targets of XYD were determined via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the target proteins were chosen through the Uniprot database. GeneCards, Online Mendelian Inheritance in Man, and Drugbank were utilized to identify gene targets associated with UAN, whereas Venny 2.1.0 was employed to determine the common intersections between medication targets and disease targets. Cytoscape 3.7.1 was employed to map the network of active substances in Traditional Chinese medicine and their potential targets, while the protein-protein interaction network was constructed using the String database and Cytoscape software to identify critical target proteins. Gene ontology annotation analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed using R version 4.0.0 software . A total of 206 active components were identified from the XYD, of which 62 were recognized as possible therapeutic targets. We screened out 31 key targets by the protein-protein interaction network. Gene ontology enrichment analysis revealed 81 biological processes, 14 cellular components, and 96 molecular functions. Kyoto encyclopedia of genes and genomes enrichment analysis showed that 199 pathways were significantly enriched, whose functions were mainly involved in immune system, endocrine system, cell death and autophagy, and other biological processes. The molecular docking data indicated that the binding energy between the active components of XYD and the major targets exhibited significant binding affinity. The mechanism of XYD in treating UAN involves multiple components, multiple targets, and multiple pathways, including participating in lipid metabolism, inhibiting inflammation, regulating apoptosis and autophagy. The study also found that FOXO signal pathway may be a potential pathway for treating UAN. Additionally, a novel therapeutic approach for UAN has been established, targeting various signaling pathways.