Title : Aqueous extract of Ceratonia siliqua L. leaves elicits antioxidant, anti-inflammatory, and AChE inhibiting effects in amyloid-beta42-induced cognitive deficit mice: Role of alpha7-nAChR in modulating Jak2\/PI3K\/Akt\/GSK-3beta\/beta-catenin cascade - El Sayed_2023_Phytother.Res__ |
Author(s) : El Sayed NS , Abidar S , Nhiri M , Hritcu L , Ibrahim WW |
Ref : Phytother Res , : , 2023 |
Abstract :
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder attributed to several etiological factors including cholinergic dysregulation, neuroinflammation, oxidative stress, beta-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-beta42 (Abeta42) injection in mice. Abeta42-injected mice were treated with Cs (100 mg/kg/day, po) with or without methyllycaconitine (MLA; 1 mg/kg/day, ip), an alpha7-nAChR antagonist. Abeta42-injected animals demonstrated an elevation of hippocampal Abeta42, p-Tau, and acetylcholinesterase. They also showed a decline in phosphorylated levels of Jak2, PI3K, Akt, and GSK-3beta, 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-kappaBp65 and TNF-alpha, while elevating Nrf2 and HO-1, along with stabilizing beta-catenin under the impact of Jak2/PI3K/Akt/GSK-3beta signaling. These beneficial effects of Cs were abrogated by MLA co-administration signifying the alpha7-nAChR involvement in Cs-mediated effects. Therefore, Cs can ameliorate Abeta42-induced neurodegeneration by modulating Jak2/PI3K/Akt/GSK-3beta/beta-catenin axis in an alpha7-nAChR-dependent manner. |
PubMedSearch : El Sayed_2023_Phytother.Res__ |
PubMedID: 36760217 |
El Sayed NS, Abidar S, Nhiri M, Hritcu L, Ibrahim WW (2023)
Aqueous extract of Ceratonia siliqua L. leaves elicits antioxidant, anti-inflammatory, and AChE inhibiting effects in amyloid-beta42-induced cognitive deficit mice: Role of alpha7-nAChR in modulating Jak2\/PI3K\/Akt\/GSK-3beta\/beta-catenin cascade
Phytother Res
:
El Sayed NS, Abidar S, Nhiri M, Hritcu L, Ibrahim WW (2023)
Phytother Res
: