Piperine Prevents Scopolamine-Induced Cognitive Impairment via its Antioxidant and Anti-Inflammatory Roles;...

Alzheimer's disease (AD) is the leading cause of dementia, characterized by cognitive decline and neurodegeneration. Given the limitations of current treatments, research has turned to natural substances such as piperine, which is known for its neuroprotective properties. This study investigates the effects of piperine on cognitive function and genes associated with oxidative stress, inflammation, and necroptosis-related genes in a rat model of cognitive impairment. Fifty adult male Wistar rats were used, divided into five groups: an intact group, a control group (vehicle solution followed by scopolamine), and three experimental groups receiving piperine (5, 10, and 20 mg/kg) followed by scopolamine during the training period. Behavioral assessment was conducted using the Morris Water Maze (MWM) test. Hippocampal tissue was collected after euthanasia for gene expression analysis of Nrf2, HO‑1, TNF‑α, Fas, TRAIL, MLKL, and Caspase‑8. Spatial learning and memory improved significantly in piperine-treated groups, with no impact on swimming velocity, indicating cognitive enhancement without affecting motor functions in the scopolamine-induced cognitive impairment model. Piperine pretreatment prevented oxidative stress and inflammation, as evidenced by the restoration of Nrf2, HO-1, and Caspase-8 and the reduction of TNF-α, Fas, TRAIL, and MLKL expression levels. These findings suggest that piperine has antioxidative, anti‑inflammatory, and cognitive‑enhancing effects, with particular effects possibly on necroptosis, and could be a valuable addition to the current AD treatment paradigm, warranting further investigation in clinical trials.