Objective To explore the potential targets and mechanism of formononetin in the treatment of atherosclerotic plaque treatment based on network pharmacological study.Methods The target genes of formononetin were obtained from PubChem and other databases;the target genes of carotid atherosclerotic plaques were obtained from GeneCards and DisGeNET databases,then screened and combined with those extracted from GEO gene chip.The target genes shared by the drug and the disease were obtained through Venn diagrams and enriched by R software package.The protein interactions network of the shared targets was constructed by String online platform,and the core targets were obtained by screening the topological parameters of the network with Cytoscape software;the binding activities of the screened core targets with formononetin were verified by molecular docking technology.The core targets of CAP1,CXCL8,EGFR,FOS,KDR,IGF1,MMP9,and PPARG were screened,and the molecular docking simulation showed that these core targets had strong binding activities with formononetin.Results A total of 413 action targets of formononetin and 1 244 differentially expressed genes in carotid atherosclerotic plaque were screened out.Based on the interaction analysis,55 potential targets related to the effect of formononetin on carotid atherosclerotic plaques were obtained.KEGG enrichment analysis showed that the genes were significantly enriched in PPAR signaling pathway,MAPK signaling and other pathways,and the gene-function were mostly related to inflammation and apoptotic cells.The core targets CAP1,CXCL8,EGFR,FOS,CTSS,IGF1,MMP9 and PPARG were obtained by Cytoscape screening,and the molecular docking simulation showed that their core targets had strong binding activities with formononetin.Conclusion Formononetin acts on multiple core targets such as CAP1 to regulate inflammation-related signaling pathways,thereby exerting an effect on preventing the arterial plaque formation,which provides support for subsequent clinical drug development.
万方数据
维普
