SVHRSP alleviates age-related cognitive deficiency by reducing oxidative stress and neuroinflammation through Sirt 1 pathway

Background Our previous studies have shown that Scorpion venom heat-resistant synthesized peptide (SVHRSP) exhibits a significant extension in lifespan and improve in age-related physiological functions in worms. However, the mechanism underlying the potential anti-aging effects of SVHRSP in mammals remains elusive. Methods After conducting behaviour test, brain tissues were collected for morphological analysis, electrophysiology experiments, flow cytometry and protein or gene expression following SVHRSP treatment. H ₂ O ₂ -induced cell model was used to investigate the involvement of Sirt1 in the regulation of oxidative stress and inflammation mediated by SVHRSP. Results SVHRSP significantly ameliorated age-related cognitive decline, enhanced long-term potentiation, restored the synaptic loss, and upregulated the expression of synaptic proteins, thereby, indicating an improvement in synaptic plasticity. Moreover, SVHRSP demonstrated a decline in senescent markers, including SA-β-gal enzyme activity, p16, p12, Sirt1 and cell cycle arrest. The underlying mechanism involve an upregulation of antioxidant enzyme activity and a reduction in oxidative stress-induced damage. Furthermore, SVHRSP regulated the nucleoplasmic distribution of Nrf2 through sirt1-p53 pathway. Further research indicated that a reduction in the expression of pro-inflammatory factor in the brain after SVHRSP treatment. SVHRSP attenuated neuroinflammation by regulating the NF-κB nucleoplasmic distribution and inhibiting microglia and astrocytes activation through Sirt1-NF-κB pathway. Additionally, SVHRSP significantly augmented Nissl bodies count while suppressing the neuronal loss. Conclusion SVHRSP could remarkably improve cognitive deficiency by inhibiting oxidative stress and neuroinflammation through the activation of Sirt 1 pathway, thus representing an effective strategy to improve brain health.