Objective To explore the potential active ingredients and mechanism of polygonatum sibiricum(PS)in regulating ferroptosis in Alzheimer's disease(AD)based on bioinformatics.Methods Utilized the TCMSP and UniProt databases to screen active ingredients and determine the effect targets in PS.The targets for AD were retrieved from GeneCards,DrugBank,TTD and GEO databases.Venny diagram was performed to identify potential targets of PS being treated on AD.The network diagram,illustrating the interactions among PS,its active ingredients and targets,was constructed using Cytoscape 3.9.1,with protein-protein interaction(PPI)obtained from the STRING database.The targets were subjected to gene ontology(GO)enrichment and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis using the Metascape database,then visualized.Ferroptosis genes were sourced from the FerrDb database and furthermore,the key targets and KEGG pathway were performed.Molecular docking and visualization were carried out using AutoDockTools to elucidate the interaction between active ingredients of PS and key targets.Results Identified 18 active ingredients in PS,109 potential targets involved in treating AD with PS,13 potential targets associated with ferroptosis in AD,and 4 key targets of PS regulating ferroptosis in anti-AD,including androgen receptor(AR),hypoxia-inducible factor-1(HIF-1),E3 ubiquitin-protein ligase mdm2(MDM2),and tumor protein 53(TP53).The KEGG pathway of the key targets mainly focused on cancer,HIF-1 signaling pathway,IL-17 signaling pathway,chemical carcinogenic-receptor activation and other signaling pathways.Molecular docking demonstrated strong binding affinity between PS active ingredients,including Diosgenin,Baicalein,Apigenin,Isoliquiritigenin,3'-Methoxydaidzein,4',5-Dihydroxyflavone,and the key targets.Conclusion Polygonatum sibiricum may alleviate and improve AD by regulating ferroptosis using diosgenin,baicalein,apigenin,isogliquiritin,3'-methyldaidzein,4',5-dihydroxyflavone.The mechanism may involve the regulation of AR,HIF-1,MDM2,TP53 protein expression,and related pathways.
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