Alleviation of renal ischemia-reperfusion injury by quercetin, kaempferol, and myricetin in Shiwei Hezi pill (SHP): Network pharmacology and molecular docking analysis of a traditional Tibetan herbal agent

The aim of the study was to utilize a systematic network pharmacology approach to explore the active components, targets, and pathways associated with the efficacy of Shiwei Hezi pill (SHP) in treating renal ischemia-reperfusion injury (RIRI). We utilized online databases to identify common targets of SHP and RIRI. Functional annotation of genes using the Gene Ontology (GO) and enrichment analysis of pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed using bioinformatics websites. Cytoscape was utilized to generate and visualize protein-protein interaction (PPI) networks. We employed specialist software to conduct molecular docking analysis on crucial constituents and targets in order to validate the interaction patterns between core ingredients and essential targets. We screened 54 ingredients with good bioavailability in SHP and identified 204 shared targets between SHP and RIRI. Our data suggests that SHP may primarily target TNF, IL6, GAPDH, MMP9, PTGS2, and MMP6 in the therapeutic management of RIRI. The GO enrichment and KEGG pathway enrichment show that the mechanism of SHP treatment for RIRI involves multiple biological processes and signaling pathways. The molecular docking indicates that the three most potent active components of SHP (quercetin, kaempferol, and luteolin) have a strong likelihood of binding to TNF, IL6, GAPDH, MMP9, and PTGS2 with a high degree of affinity. This is the first exploration of the potential mechanism of Tibetan medicine formula SHP in treating RIRI using network pharmacology. Our research indicates that the various components of SHP could act on multiple targets and signaling pathways associated with RIRI. The findings in this study provide a theoretical basis and a novel method for the clinical therapy of RIRI.