Argininyl-fructosyl-glucose (AFG) antagonizes D-galactose-induced cellular senescence of neuro-2a via inhibiting endoplasmic reticulum stress and apoptosis

Argininyl-fructosyl-glucose (AFG), a distinctive non-saponin compound isolated from red ginseng (Panax ginseng. C.A. Meyer), demonstrates neuroprotective effects. However, the molecular mechanism underlying AFG's anti-aging properties remains unclear. This study established an in vitro D-galactose-induced N2a cells subacute aging model to investigate AFG's anti-aging activity and potential mechanisms. Results indicated that AFG treatment (8 μM) significantly reduces the overexpression of aging-related proteins (p53/p21/p16) induced by D-galactose, highlighting its anti-aging efficacy. AFG concurrently diminishes ROS accumulation, lowering extracellular lactate dehydrogenase and alleviating intracellular oxidative stress. Notably, AFG suppresses the PERK/CHOP/caspase 12 pathway, reducing intracellular Ca2+ concentration and mitigating endoplasmic reticulum (ER) stress. Additionally, AFG decreases Bax and caspase 3 expression, elevates Bcl-2 and mitochondrial membrane potential, mitigating apoptosis. NAC with 4-PBA validated the results. Overall, AFG protects N2a cells from aging by reducing ER stress and apoptosis, suggesting its potential as a key substance for treating aging and neurodegenerative diseases.