Based on network pharmacology to explore the mechanism of nephrotoxicity of Xanthii Fructus

摘要

Objective:To explore the potential mechanism of nephrotoxicity induced by Xanthii Fructus(XF)through network pharmacology.Methods:The active ingredients and targets of XF were screened through Traditional Chinese Medicine Systems Pharmacology Database,PubChem Database and Swiss Target Prediction Database,and the related pathogenic genes of nephrotoxicity were downloaded from Genecards,pharmGKB and OMIM databases.The potential target is the intersection of XF and the pathogenic gene of nephrotoxicity.Cytoscape software was used to construct a network of“XF-Potential active ingredient-Target-Nephrotoxicity network”.Protein protein interaction(PPI)network was constructed by String database,and the data was analyzed and sorted out to obtain the key active components and core target proteins of XF.GO functional enrichment analysis and KEGG pathway enrichment analysis of key target proteins were performed by R software.Results:11 active components,167 targets,6839 nephrotoxicity related pathogenic genes and 139 intersection target genes were screened from XF.After constructing the network of“XF-Potential active ingredient-target-nephrotoxicity network”and PPI network,the key active ingredients of XF were identified as Moupinamide,Beta-sitosterol and Stigmasterol,and the core target proteins were CASP3,HSP90AA1 and TP53.There were 2072 GO entries(P<0.05),including 1876 Biological Process(BP),64 Cellular Component(CC)and 132 Molecular Function(MF).KEGG enrichment analysis revealed 138 pathways(P<0.05),mainly involving p53 signaling pathway,IL-17 signaling pathway,PI3K-Akt signaling pathway were strongly correlated with the nephrotoxicity of XF.Conclusion:The core target protein of XF HSP90AA1,CASP3 and TP53 participate in p53 signaling Pathway,PI3K-Akt signaling Pathway,IL-17 signaling Pathway and other pathways to regulate apoptosis and induce inflammatory responses,resulting in kidney damage.