Exploring the modulatory mechanisms and genetic targets of Astragalus membranaceus in inhibiting gliomas
Objective To investigate the mechanisms and genetic targets through which Astragalus membranaceus inhibits gliomas.Methods Based on network pharmacology analysis,the potential gene targets of Astragalus membranaceus for glioma were acquired.The gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis were applied to construct a protein-protein interaction(PPI)network and identify Hub genes,ultimately creating a visual network encompassing disease-drug-components-targets-pathways.Concurrently,U251 glioma cell lines were subjected to cellular experiments for validation.The impact of Astragalus membranaceus culture fluid at varying concentrations on U251 cell viability and apoptosis was assessed using a cell counting kit and live/dead cells dual staining method.Results A total of 145 potential gene targets of Astragalus membranaceus for the treatment of gliomas were identified.GO enrichment analysis revealed the predominant biological functions,including binding of different proteins,binding of identical proteins,positive regulation of transcription from RNA polymerase Ⅱ promoter,enzyme binding,etc.Meanwhile,KEGG pathway analysis revealed the principal signaling pathways,encompassing pathways in cancer,lipid and atherosclerosis,fluid shear stress and atherosclerosis,chemical carcinogenesis-receptor activation,etc.The Hub genes were ranked in descending order of association intensity as VEGFA,protein kinase B(AKT)1,JUN,MMP9,PTGS2,IL-6,IL-1B,CASP3,TP53,and HIF1A.Among all bioactive constituents,MOL000098(quercetin)exhibited the highest centrality,with a degree value of 118.Within the spectrum of signaling pathways,hsa05200(cancer pathway)attained the highest degree value,reaching 61.Amongst all gene targets,AKT1,RELA,PTGS2,MAPL1 and TP53 demonstrated elevated centrality,with degree values of 21,20,20,19 and 18,respectively.Cellular experiments validated that Astragalus membranaceus culture fluid at different concentrations(1,5,10 mg/mL)exerted inhibitory and apoptotic effects on U251 cell proliferation,with the intensity of its effects exhibiting concentration dependency(all P＜0.05).Conclusion Astragalus membranaceus demonstrates inhibitory and apoptotic effects on U251 cell proliferation,with primary gene targets including AKT1,RELA,PTGS2,MAPL1,and TP53.
Astragalus membranaceusGliomaNetwork pharmacologyTarget genesMechanism of actionCell experiment
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维普
