Aqueous extract of Ceratonia siliqua L. leaves elicits antioxidant, anti-inflammatory, and AChE inhibiting effects in amyloid-β42-induced cognitive deficit mice: Role of α7-nAChR in modulating Jak2/PI3K/Akt/GSK-3β/β-catenin cascade.

Autor: El Sayed NS; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt., Abidar S; Laboratory of Biochemistry and Molecular Genetics (LBMG), Faculty of Sciences and Technologies of Tangier (FSTT) Abdelmalek Essaadi University, Tetouan, Morocco., Nhiri M; Laboratory of Biochemistry and Molecular Genetics (LBMG), Faculty of Sciences and Technologies of Tangier (FSTT) Abdelmalek Essaadi University, Tetouan, Morocco., Hritcu L; Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, Iasi, Romania., Ibrahim WW; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Phytotherapy research : PTR [Phytother Res] 2023 Jun; Vol. 37 (6), pp. 2437-2453. Date of Electronic Publication: 2023 Feb 09.
DOI: 10.1002/ptr.7766
Abstrakt: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder attributed to several etiological factors including cholinergic dysregulation, neuroinflammation, oxidative stress, β-amyloidogenesis, and tauopathy. This demands the search for multitarget drugs, especially of natural sources owing to their pleiotropic activities and low adverse effects. The present study was conducted to investigate the cognitive-improving potential of Ceratonia siliqua L. (Cs) extract compared with donepezil, an acetylcholinesterase inhibitor, on AD-like pathological alterations induced by single intracerebroventricular amyloid-β42 (Aβ42) injection in mice. Aβ42-injected mice were treated with Cs (100 mg/kg/day, po) with or without methyllycaconitine (MLA; 1 mg/kg/day, ip), an α7-nAChR antagonist. Aβ42-injected animals demonstrated an elevation of hippocampal Aβ42, p-Tau, and acetylcholinesterase. They also showed a decline in phosphorylated levels of Jak2, PI3K, Akt, and GSK-3β, leading to induction of neuroinflammation and oxidative stress. Noteworthy, Cs improved the histopathological and behavioral variables in addition to mitigating AD hallmarks. It also exerted neuroprotection by reducing NF-κBp65 and TNF-α, while elevating Nrf2 and HO-1, along with stabilizing β-catenin under the impact of Jak2/PI3K/Akt/GSK-3β signaling. These beneficial effects of Cs were abrogated by MLA co-administration signifying the α7-nAChR involvement in Cs-mediated effects. Therefore, Cs can ameliorate Aβ42-induced neurodegeneration by modulating Jak2/PI3K/Akt/GSK-3β/β-catenin axis in an α7-nAChR-dependent manner.
(© 2023 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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