The Potential Mechanism of Quercetin in Treating Diabetic Foot Ulcer Revealed by Network Pharmacology

Introduction: To identify the critical genes, biological mechanisms, and signaling pathways involved in the therapeutic effects of quercetin on diabetic foot ulcers using network pharmacology and molecular docking approaches. Methods: We identified pathological targets of diabetic foot ulcers (DFU) from Gene- Cards, OMIM, and TTD, and pharmacological targets of quercetin from STP, TCMSP, and PharmMapper. Intersection analysis revealed potential therapeutic targets. Core targets were determined via GO/KEGG enrichment, PPI network construction, and Cytoscape screening algorithms (Degree, Closeness, Betweenness). Molecular docking and dynamics simulations assessed quercetin-core target interactions and binding affinity. Results: After screening and intersecting the targets of quercetin and diabetic foot ulcers, 236 genes related to quercetin';s anti-diabetic foot ulcer effects were identified, with six key genes emerging as critical: SRC, TP53, MAPK1, JUN, HSP90AA1, and AKT1. Enrichment analysis suggested that quercetin may modulate inflammatory imbalance(HSP90AA1), immunosuppression(JUN), and oxidative stress(SRC, TP53, MAPK1, and AKT1) during diabetic foot ulcer progression. Discussion: The relationship between these core targets and biological pathways in diabetic foot ulcers requires further experimental validation. Notably, molecular docking and dynamics simulation results confirmed strong binding affinity between quercetin and the core targets, supporting their potential therapeutic relevance. Conclusion: Quercetin exerts anti-diabetic foot ulcer effects by regulating SRC, TP53, MAPK1, JUN, HSP90AA1, and AKT1. These hub genes may serve as promising candidates for future therapeutic interventions in diabetic foot ulcers.