Network pharmacology and molecular docking-based systemic approach to investigate the mechanism and molecular targets of phloridzin against Alzheimer's disease

To explore the potential targets of phloridzin against Alzheimer's disease using network pharmacology and bioinformatic approach, Phloridzin's target genes have been retrieved from public databases (PharmMapper, Swiss Target Prediction, Targetnet and SuperPred). Alzheimer's disease targets were retrieved from Genecards and DisGeNet, a disease database. Using STRING and Cytoscape, protein -protein interaction networks (PPI) were generated and hub genes were found using topological analysis and MCODE. Target protein annotation was done using functional enrichment analysis from the Kyoto Encyclopedia and Genome Database (KEGG) and Gene Ontology (GO). The Discovery studio visualizer was used to further visualize the molecular docking of phloridzin with the hub genes using Autodock tools. Phloridzin's efficacy in treating Alzheimer's has been associated with thirty-eight targets. GSR, GAPDH, ACE, NOS3, HMOX1, GSK3B, ESR1, MAPK1, BACE1 and PPARG were key targets. 500 biological processes (BP), 65 cellular components (CC) and 142 molecular functions (MF) were identified from the results of the GO functional enrichment analysis. KEGG pathway enrichment analysis discovered 117 signaling pathways (P<0.05) including highly enriched pathways like the "AGE -RAGE signaling pathway" and the "HIF-1 signaling pathway". Molecular docking of phloridzin with hub genes revealed a highly stable structure with lower binding affinity values. Phloridzin can regulate various signaling pathways and have a therapeutic effect against AD.