p‐Coumaric acid protects against D‐galactose induced neurotoxicity by attenuating neuroinflammation and apoptosis in mice brain

D-galactose (D-gal) induced senescence in rodents is a widely used Alzheimer's model. Chronic administration of D-gal causes neuroinflammation leading to cognitive deficit and memory impairment.Present study investigated the neuroprotective effects of the natural phenol, p-Coumaric acid (PCA) and its underlying mechanism against the chronic D-gal induced senescence in Swiss albino mice. D-gal (150 mg/kg) was administration s.c.ly to mice for 42 consecutive days.D-gal produced cognitive impairment as observed in Morris water maize (MWM) and Y maze test, which was ameliorated by concurrent treatment with PCA (80 mg/kg, and 100 mg/kg, p.o.). Importantly, PCA treatment attenuated the D-gal induced oxidative stress and significantly inhibited acetylcholinesterase (AChE) activity in mice brain. Furthermore, PCA treatment significantly lowered levels of inflammatory marker nuclear factor kappa B (NFκB) and reduced levels of proapoptotic enzyme caspase 3. We also observed that PCA treatment exhibited β-secretase enzyme (BACE1) inhibitory effect. However, PCA treatment failed to decrease the level of advanced glycation end products (AGE) both in vitro and in vivo.Current study demonstrated the significant neuroprotective effect of PCA against D-galactose induced neuroinflammation, cognitive impairment and apoptosis.