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

Alzheimer's disease (AD) hallmarks include amyloid-beta eta (A beta) 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-3 beta pathway. The experiment was performed on 70 male Wistar albino rats divided into seven groups (control, NCMN, Donepezil, AD-model, Donepezil cotreatment, 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, beta-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-3 beta) and toll-like receptor-4 were evaluated. Treatment with NCMN improved memory, locomotion, neuronal differentiation by activating PI3K/AKT/GSK-3 beta pathway. These results were confirmed by histological studies in hippocampus.

Automated summary

This study aimed to evaluate the protective role of nanocurcumin as an antioxidant and anti-inflammatory agent, and its synergistic effects with Donepezil in the treatment of Alzheimer's disease in rats. The results showed that treatment with nanocurcumin improved memory, locomotion, and neuronal differentiation by activating the PI3K/AKT/GSK-3 beta pathway.