Kaur_2025_J.Neuroimmunol_406_578682

Exposure to chronic unpredictable stress (CUS) serves as the major contributor for the neurobehavioral changes. The current study explores the possible involvement of the SIRT1 pathway in mediating the neuroprotective properties of piceatannol in CUS induced neurobehavioral changes. Molecular docking studies showed binding interactions of piceatannol with SIRT1, suggesting that it may modulate SIRT1 activity. For evaluating effect of CUS and pharmacological interventions on neurobehavioral changes, the mice (Swiss Albino, Male) were subjected to the EPM, TST, FST, SPT, MWM and PA test. In current study, the effect on levels of corticosterone and neurotransmitters (dopamine and serotonin); various parameters of oxidative stress and neuroinflammation; acetylcholinesterase and histological changes in hippocampus and cortex were also assessed. It was observed that piceatannol (10 and 20 mg/kg; p.o) reduced the deleterious impact of CUS on oxidative stress and neuroinflammation; reduced corticosterone and dopamine levels; increased serotonin levels and improved neurobehavioral and histological changes. Pre-treatment with sirtinol (10 mg/kg; i.p.), a SIRT1 inhibitor, greatly reduced the neuroprotective properties of piceatannol. Thus, it may be concluded that activation of SIRT1 pathway may be responsible for the neuroprotective effects of piceatannol on CUS induced neurobehavioral alterations.