Alzheimer's disease (AD) hallmarks include amyloid-βeta (Aβ) and tau proteins aggregates, neurite degeneration, microglial activation with cognitive impairment. Phosphatidylinositol-3-kinase/protein kinase B/Glycogen synthase kinase-3-beta (PI3K/AKT/GSK-3) pathway is essential for neuroprotection, cell survival and proliferation by blocking apoptosis. This study aimed to assess protective role of nanocurcumin (NCMN) as strong antioxidant and anti-inflammatory agent with elucidating its synergistic effects with Donepezil as acetylcholinesterase inhibitor on AD in rats via modulating PI3K/AKT/GSK-3β pathway. The experiment was performed on 70 male Wistar albino rats divided into seven groups (control, NCMN, Donepezil, AD-model, Donepezil co-treatment, NCMN only co-treatment, and NCMN+Donepezil combined treatment). Behavioral and biochemical investigations as cholinesterase activity, oxidative stress (malondialdehyde, reduced glutathione, nitric oxide, superoxidedismutase, and catalase), tumor necrosis factor-alpha, Tau, β-site amyloid precursor protein cleaving enzyme-1 (BACE-1), Phosphatase and tensin homolog (Pten), mitogen-activated protein kinase-1 (MAPK-1), Glycogen synthase kinase-3-beta (GSK-3β) and toll-like receptor-4 were evaluated. Treatment with NCMN improved memory, locomotion, neuronal differentiation by activating PI3K/AKT/GSK-3β pathway. These results were confirmed by histological studies in hippocampus.

阿尔茨海默氏病 (AD) 的标志包括淀粉样蛋白-βeta (Aβ) 和 tau 蛋白聚集、神经突变性、小胶质细胞激活并伴有认知障碍。磷脂酰肌醇-3-激酶/蛋白激酶 B/糖原合成酶激酶-3-β (PI3K/AKT/GSK-3) 途径通过阻断细胞凋亡对于神经保护、细胞存活和增殖至关重要。本研究旨在评估纳米姜黄素 (NCMN) 作为强抗氧化剂和抗炎剂的保护作用，并阐明其与乙酰胆碱酯酶抑制剂多奈哌齐通过调节 PI3K/AKT/GSK-3β 通路对 AD 大鼠的协同作用。实验对象为 70 只雄性 Wistar 白化大鼠，分为七组（对照组、NCMN、多奈哌齐、AD 模型、多奈哌齐联合治疗、仅 NCMN 联合治疗、NCMN+多奈哌齐联合治疗）。行为和生化研究，如胆碱酯酶活性、氧化应激（丙二醛、还原型谷胱甘肽、一氧化氮、超氧化物歧化酶和过氧化氢酶）、肿瘤坏死因子-α、Tau、β-位淀粉样前体蛋白裂解酶-1 (BACE-1)、磷酸酶评估了张力蛋白同系物 (Pten)、丝裂原激活蛋白激酶 1 (MAPK-1)、糖原合成酶激酶 3-β (GSK-3β) 和 Toll 样受体 4。NCMN 治疗通过激活 PI3K/AKT/GSK-3β 通路改善记忆、运动和神经元分化。这些结果得到了海马组织学研究的证实。