Astaxanthin-s-allyl cysteine diester against high glucose-induced neuronal toxicity in vitro and diabetes-associated cognitive decline in vivo: Effect on p53, oxidative stress and mitochondrial function.

Neuroprotective effect of astaxanthin-s-allyl cysteine diester (AST-SAC) against high glucose (HG)-induced oxidative stress in in vitro and cognitive decline under diabetes conditions in in vivo has been explored. Pretreatment of AST-SAC (5, 10 and 15 μM) dose-dependently preserved the neuronal cells (SH-SY5Y) viability against HG toxicity through i) decreasing oxidative stress (decreasing reactive oxygen species generation and increasing endogenous antioxidants level); ii) protecting mitochondrial function [oxidative phosphorylation (OXPHOS) complexes activity and mitochondrial membrane potential (MMP)]; and iii) decreasing p53 level thereby subsequently decreasing the level of apoptotic marker proteins. Male Spraque-Dawley rats were orally administered AST-SAC (1 mg/kg/day) for 45 days in streptozotocin-induced diabetes mellitus (DM) rats. AST-SAC administration prevented the loss of spatial memory in DM rats as determined using the novel object location test. AST-SAC administration alleviated the DM-induced injury in brain such as increased cholinesterases activity, elevated oxidative stress and mitochondrial dysfunction. Altogether, the results from the present study demonstrated that AST-SAC averted the neuronal apoptosis and preserved the cognitive function against HG toxicity under DM conditions.