Ahsan_2025_Brain.Res__149650

BACKGROUND: The study aimed to evaluate Plumbagin's neuroprotective potential against scopolamine-induced Alzheimer's disease, proposing that its effects may involve GSK-3beta inhibition, a key factor in tau hyperphosphorylation, to promote neuroprotection in Wistar rats. METHODS: Alzheimer's was induced in male Wistar rats. After acclimatization, the rats were subjected to daily intraperitoneal treatment with scopolamine (0.7 mg/kg) and oral administration of Plumbagin (10 mg/kg) for 13 days. The cognitive function of treated rats was evaluated using the Morris water maze test, along with assessments of locomotor activity, acetylcholinesterase activity (AChE), protein levels, antioxidant parameters, cytokines and Brain-Derived Neurotrophic Factor (BDNF) and brain histopathology (hippocampus). RESULTS: The Plumbagin (10 mg/kg, oral) as given orally significantly improved neurobehavioral alterations compared to Alzheimer's induced group. Scopolamine impaired cognitive function and increased locomotor activity ((#)P < 0.05). Treatments improved Morris water maze performance, reducing Escape latency time and increasing Time spent in the target quadrant (*P < 0.05). Biochemically, treatments significantly improved BDNF (*P < 0.05), decreased AChE activity, oxidative stress, reduced Interleukin-6 and Tumor Necrosis Factor Alpha (*P < 0.05) and reversed Scopolamine induced hippocampal neuronal loss ((##)P < 0.01). Plumbagin showed significant (*P < 0.05) neuroprotective effects, improving cognitive function, reducing AChE activity, Malondialdehyde, oxidative stress, and neuroinflammatory markers exceeding individual treatments in the scopolamine-induced Alzheimer's disease model. These improvements suggest a possible mechanism through the inhibition of GSK-3beta, which may contribute to the observed neuroprotective effects. CONCLUSION: This study suggests that Plumbagin's neuroprotective effects in scopolamine-induced Alzheimer's disease may involve GSK-3beta inhibition. Plumbagin shows significant therapeutic potential for Alzheimer's treatment, warranting further investigation of its mechanism.