Exploring mechanism of Wuzi Yanzong Pills in treating hepatic fibrosis based on network pharmacology and molecular docking
Objective The mechanism of the kidney-tonifying formula Wuzi Yanzong Pills was explored in treatment of hepatic fibrosis by means of network pharmacology and molecular docking technology.Method The active components of Wuzi Yanzong Pills and it's corresponding targets were predicted by Using TCMSP database and the target names were standardized through the Uniprot database.The hepatic fibrosis targets were collected through OMIM,Gene Cards,and DisGeNET databases,the potential targets of Wuzi Yanzong Pills in treatment of liver fibrosis were obtained by the intersection of active component targets and disease targets selected by Venn diagram.Cytoscape 3.9.0 software was used to map the active components-intersection targets-disease network and to predict core targets.STRING platform was used to construct a PPI network.Pathway enrichment was analyzed by gene ontology(GO)function and Kyoto encyclopedia of geneses and genomes(KEGG);AutoDockTools software was used to dock the core target with active components.Result 84 active components of Wuzi Yanzong Pills and 179 potential targets of the active components were obtained,798 hepatic fibrosis targets and 81 intersection targets between the disease and Wuzi Yanzong Pills were identified.26 active components and 37 key targets for the treatment of hepatic fibrosis by Wuzi Yanzong Pills were screened by meridian topology analysis.Quercetin,kaempferol,matrine,and glycitein were important active components of Wuzi Yanzong Pills in treating hepatic fibrosis which were predicted by the"active ingredient target pathway"network.The core targets were RAC-αSerine/threonine protein kinase(AKT1),tumor necrosis factor(TNF),interleukin-6(IL6),cell tumor antigen p53(TP53),vascular endothelial growth factor A(VEGFA),etc.The biological process of GO functional enrichment analysis were mainly related to the positive regulation of RNA polymerase Ⅱ promoter transcription and gene expression,the cellular components were closely related to the extracellular space,nucleus,etc.,the molecular function was mainly related to the binding of macromolecular complexes,protein kinase activity,and specific DNA binding to the proximal sequence of RNA polymerase Ⅱ core promoter.The main pathways through which Wuzi Yanzong Pills treated hepatic fibrosis include the chemical carcinogenic reactive oxygen species signaling pathway,JAK-STAT signaling pathway,PI3K-Akt signaling pathway,MAPK signaling pathway,etc.The core components of quercetin,kaempferol,matrine,and glycitein had stable docking and binding with core targets such as AKT1,TNF,IL6,VEGFA,CASP3,etc.Molecular docking had preliminarily demonstrated that key components spontaneously bind to multiple core proteins and can regulate multiple key targets.Conclusion The mechanism of the kidney-tonifying formula Wuzi Yanzong Pills in treatment of hepatic fibrosis was preliminarily revealed that it could interfere the the process of apoptosis through positive and negative regulation,oxidative stress,inflammatory factors,angiogenesis,and other response;The kidney tonifying formula Wuzi Yanzong Pills had the characteristics of multiple components,multiple targets,and multiple pathways,which can provide a reference basis for emphasizing the kidney tonifying method in the clinical treatment of hepatic fibrosis.