Abstract:This study investigated the anti-aging mechanism of quercitrin using Caenorhabditis elegans experiments combined with network pharmacology approaches. C. elegans were treated with varying concentrations of quercitrin to assess its effects on lifespan，locomotor behavior，stress resistance，and antioxidant enzyme activity. Drug targets were screened using the PharmMapper and SwissTargetPrediction platforms，and aging-related targets were identified from the Genecards database. A protein-protein interaction （PPI） network was constructed to identify core targets，followed by Gene Ontology （GO） functional and Kyoto Encyciopedia of Genes and Genomes （KEGG） pathway enrichment analyses using the database for annotation，visualization and integrated discovery （DAVID） database. Molecular docking validation was performed using AutoDock. Quercitrin treatment significantly extended the lifespan of C. elegans （P＜0.05），enhanced resistance to thermal and oxidative stress （stress resistance indicators increased by 23.6%-41.2%），and boosted the activity of superoxide dismatase （1.8-fold） and catalase （CAT）（2.1-fold）. Network analysis identified five core targets，including epidermal growth factor receptor （EGFR），AKT serine/threonine kinase 1（AKT1），and mitogen-activated protein kinase 1（MAPK1）. KEGG enrichment revealed significant enrichment in metabolic regulation pathways （hsa01100） and signaling pathways （hsa05200）（false discovery rate＜0.01）. Molecular docking demonstrated that quercitrin exhibited binding energies of less than -6.0 kcal/mol with core targets，with a binding energy of-8.4kcal/mol for EGFR （PDB：2ITX），forming a stable hydrogen bond network.