Exploring the Potential Molecular Targets of Cyanidin-3-O-glucoside for Type 2 Diabetes Mellitus Treatment.
INTRODUCTION: This study aims to elucidate the multi-target molecular mechanism of cyanidin-3-O-glucoside (C3G) in treating Type 2 Diabetes (T2DM) through network pharmacology methods. METHODS: The study was designed to predict the targets of C3G through public databases and to screen for T2DM-related targets. Protein-protein interaction (PPI) network analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the common targets. Core targets were further validated through molecular docking and molecular dynamics (MD) simulations. RESULTS: This research identified a total of 57 potential targets of C3G in the treatment of T2DM. Subsequent PPI analysis identified ALB (Degree=43), AKT1 (Degree=41), and TNF (Degree=41) as the top three hub proteins. Pathway analysis indicated significant involvement in the insulin signaling pathway (P = 4.205×10-9), AMPK signaling pathway (P = 9.582×10-7), and FoxO signaling pathway (P = 1.315×10-6). Molecular docking revealed strong binding affinities between C3G and NOS3 (-9.5 kcal/mol), PPARG (-9.0 kcal/mol), TNF (-8.5 kcal/mol), and INSR (-8.4 kcal/mol). MD simulations further confirmed that the C3G-target complex has excellent binding stability. DISCUSSION: C3G may intervene in the pathological progression of T2DM by regulating key pathways such as insulin sensitivity, inflammatory responses, and oxidative stress. Further studies suggest that INSR and NOS3 may be new targets through which C3G exerts its effects, but their specific mechanisms and in vivo biological functions still need to be elucidated by subsequent experiments. CONCLUSION: C3G may intervene in the progression of T2DM in a multi-pathway synergistic manner by targeting key molecules such as INSR and NOS3.