AFG Ameliorates Diabetic Retinopathy through AMPK-Dependent Autolysosomal Pathway: From Network Pharmacology to In Vivo and In Vitro Validation

Diabetic retinopathy (DR) is a sight-threatening microvascular complication of diabetes. This study investigates the protective effects and mechanisms of arginyl-fructosyl-glucose (AFG) (a hypoglycemic component from red ginseng) against DR. Utilizing network pharmacology and experimental models (HFD/STZ-induced mice and high-glucose-stimulated retinal cells), we demonstrate that AFG alleviates retinal injury by activating AMPK-driven autolysosome biogenesis. This core mechanism inhibits VEGF-mediated vascular hyperpermeability to preserve the blood–retinal barrier while also promoting autophagic flux, reducing lysosomal membrane permeabilization, and ultimately curtailing apoptosis. Our research results systematically clarify the various actions of AFG on DR, supporting its potential as a novel therapeutic candidate.