Study on the mechanism of quercetin in the treatment of Alzheimer's disease based on network pharmacology and experiment verification
Objective To explore the mechanism of quercetin in the treatment of Alzheimer's disease(AD)through network pharma-cology and experimental verification.Methods The targets of quercetin was screened by TCMSP,Swiss Target Prediction and UniProt database.Then the targets related to the pathogenesis of AD were obtained through TCMIP V2.0,TCMSP,TTD,Drug-Bank,CTD and DiSGeNET databases.Mapped with the target of quercetin,the obtained intersection target was used as the target of quercetin in the treatment of AD.Through String database,CytoNCA and MCODE plug-ins,the protein interaction of quercetin in the treatment of AD was carried out with the strong target as the key target of quercetin in the treatment of AD.The target of quer-cetin for AD treatment was enriched and analyzed by the Clue GO plug-in of Cytoscape 3.8.2 software and the DAVID database for GO and KEGG signaling pathway enrichment.Western blotting and real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)were used to preliminarily verify the predicted pathway.Results 230 quercetin targets were screened,43 of which coin-cided with 442 AD disease targets.The targets involved multiple biological processes and 54 signal pathways.Through cluster analy-sis and network topology parameters,6 key targets of quercetin in the treatment of AD were obtained,including glycogen synthase kinase-3β(GSK3β),vascular endothelial growth factor A(VEGFA),amyloid beta A4 protein(APP),phosphatidylinositol 3-kinase regulatory subunit alpha(PIK3R1),interleukin-6(IL6),insulin-like growth factor Ⅱ(IGF2)and transforming growth factor beta-1(TGFβ1).The results of cell experiment showed that quercetin increased the levels of AKT and GSK-3β mRNA in AD cell model and regulated the phosphorylation of AKT/GSK-3β pathway.Conclusion Quercetin can enhance the stability of injured nerve cells,improve the permeability of cell membrane,and stabilize the intracellular environment.This effect may be related to quercetin increasing the mRNA levels of AKT and GSK-3β in AD cell model and regulating the phosphorylation of AKT/GSK-3β pathway.
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