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

被引：13
作者：
Beltagy, Doha M. [1 ,4 ]
Nawar, Nagat F. [2 ]
Mohamed, Tarek M. [2 ]
Tousson, Ehab [3 ]
El-Keey, Mai M. [2 ]
机构：
[1] Damanhour Univ, Fac Sci, Biochem Dept, Damanhour, Egypt
[2] Tanta Univ, Fac Sci, Chem Dept, Biochem Div, Tanta, Egypt
[3] Tanta Univ, Fac Sci, Dept Zool, Tanta, Egypt
[4] Damanhour Univ, Fac Sci, Damanhour, Egypt
来源：
PROSTAGLANDINS & OTHER LIPID MEDIATORS | 2024年 / 170卷
关键词：
Alzheimer 's; Nanocurcumin; Oxidative stress; Donepezil; Tau protein; Cholinesterase; CURCUMIN-LOADED NANOPARTICLES; SYSTEM; CELLS; MODEL; NEUROGENESIS; ALUMINUM; MEMORY;
D O I：
10.1016/j.prostaglandins.2023.106791
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
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页数：9
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