Exploring the mechanism of Astragalus membranaceus in treating premature ovarian insufficiency:A network pharmacology and molecular docking investigation
Exploring the mechanism of Astragalus membranaceus in treating premature ovarian insufficiency:A network pharmacology and molecular docking investigation
Objective:This study aims to investigate the molecular mechanisms of Huangqi(Astragalus)in the treatment of premature ovarian insufficiency(POI)using network pharmacology and molecular docking methods.Methods:The active com-pounds and target proteins of Huangqi were screened from the TCMSP database,while the disease target proteins associated with POI were obtained from the Genecards database.The Venny online tool was used to identify the overlapping genes between the two datasets.Cytoscape software was used to construct a gene regulatory network for the active ingredients of Huangqi.The protein-protein interaction(PPI)network and core genes were selected based on the STRING database and CytoNCA plug-in of Cytoscape.GO(gene ontology)enrichment and KEGG(Kyoto encyclopedia of genes and genomes)pathway enrichment analy-ses of the overlapping genes were performed using the DAVID database.Molecular docking techniques were used to further eluci-date the molecular mechanisms underlying the therapeutic effects.Human ovarian granulosa-like tumor cells(KGN)underwent se-rum starvation(SS)treatment to induce POI cell models and then received quercetin treatment,and experimentally validated the network pharmacology prediction results by TUNEL staining and Western blotting assay.Results:The TCMSP database provid-ed 32 active compounds and 552 target genes associated with Huangqi,while totally 730 disease target genes associated with POI were screened out from the disease database.Of these,62 genes were found to be shared between the two datasets.The top 6 com-pounds based on degree values were quercetin,isorhamnetin,kaempferol,mairin,formononetin and astragaloside IV.The 10 core genes identified were ALB,INS,AKT1,ACTB,TP53,TNF,ESR1,CASP3,STAT3 and PTEN.These potential tar-gets were mainly involved in regulating the JAK2/STAT3 and PI3K/Akt signaling pathway.Molecular docking results revealed strong binding interactions between the compounds and the key proteins STAT3 and Akt1 in the JAK-STAT and PI3K-Akt sig-nalling pathways.The results of in vitro experiments revealed that quercetin could activate the JAK2/STAT3 pathway and inhibit cell apoptosis.Conclusions:Network pharmacology and molecular docking analysis showed that Astragalus could regulate the re-sponse of ovarian cells to estradiol,inhibit apoptosis and regulate the JAK-STAT and PI3K-Akt signalling pathways in the treat-ment of early onset ovarian dysfunction.
维普
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