The neuroprotective effects of SFGDI on Sirtuin3-related oxidative stress by regulating Sirt3/SOD/ROS pathway and energy metabolism in BV2 cells

Recently, the investigation of neuroprotective peptides has gained attention in addressing memory impairment and cognitive decline. Although the potential neuroprotective peptide Serine-Phenylalanine-Glycine-Aspartic-Isoleucine (SFGDI) has been identified from sea cucumber, the molecular mechanisms remain unclear. This study was to explore neuroprotection of SFGDI against 3-TYP-induced oxidative stress in BV2 cells. The result showed a retention rate of 76.70% during in vitro simulated gastrointestinal digestion and an absorption rate of 10.41% in the rat-everted gut sac model for SFGDI. Two hours following the administration of SFGDI via gavage in mice, a notable fluorescence was observed in the brain, indicating a potential neuroprotection of SFGDI through its interactions with nerve cells. Utilizing a model of oxidative stress injury induced by 3-TYP in BV2 cells, it was determined that pretreatment with SFGDI (50-200 μg/mL) resulted in the dose-dependent reduction in the acetylated SOD level leading to enhanced SOD activity and reduced level of ROS and MDA. In addition, this pretreatment triggered an increase in unsaturated lipid levels, which helped to maintain intracellular lipid metabolism balance, as well as the preservation of mitochondrial function and glycolysis levels to regulate energy metabolism. The results of this study indicate that SFGDI demonstrates neuroprotective properties through its modulation of the Sirt3/SOD/ROS pathway, regulation of lipid metabolism, and enhancement of energy metabolism in BV2 cells. These findings suggest potential novel therapeutic approaches for addressing Sirt3-related memory deficits and neurodegenerative disorders.