The synergistic effect of nanocurcumin and donepezil on Alzheimer's via PI3K/AKT/GSK-3β pathway modulating

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.