Multifaceted elucidation of aminoguanidine in protecting against diabetes-induced vascular endothelial injury

• AMG acts as a carbonyl scavenger, trapping methylglyoxal and inhibiting AGE formation, thereby preserving endothelial glycocalyx integrity. • AMG suppresses NF-κB-mediated inflammation and upregulates the eNOS/NO pathway, restoring CD31 expression and mitigating oxidative stress and apoptosis in HUVECs. • Metabolomic profiling reveals AMG's ability to modulate glutathione metabolism and the TCA cycle, alleviating MGO-induced metabolic dysregulation. • In diabetic mice, AMG improves endothelial-dependent vasodilation, reduces vascular fibrosis and basement membrane thickening, and suppresses inflammatory responses, highlighting its therapeutic potential.