Résumé
Alzheimer's disease (AD) is the most commonly diagnosed form of senile dementia, with limited therapeutic options. Neuronal damage is caused by factors secreted by inflammatory cells but also, the lack of antioxidants to prevent oxidative stress and help maintain neuronal integrity, which is crucial for cognition and memory are mediators of AD. Terminalia macroptera barks contain glycosyl terpenoids, known for their strong antioxidant properties. This study investigated the antioxidant and neuroprotective effects of the glycosylic terpenoid-rich fraction of Terminalia macroptera (GT-TeMac™) in scopolamine-treated rats. Glycosylic terpenoids were identified by LC-MS and antiradical activity tests (DPPH and ORAC) were performed. Cholinergic cognitive dysfunction and oxidative stress were induced in male wistar rats, by intraperitoneal injection of scopolamine (1 mg/kg BW/day) for seven consecutive days. GT-TeMac™ at 100 mg/kg and Donepezil at 5 mg/kg body weight were administered orally 60 min after scopolamine. After treatment, rat were sacrificed and brains were collected for the evaluation of cholinergic enzyme activity, oxidative stress markers and histopathological analysis. In vitro study was carried out to assess the ability of GT-TeMac™ to scavenge free radicals and suppress H 2 O 2 -induced ROS production in SK-N-SH cells. In addition, the ability of GT-TeMac™ to restore cell viability reduced by acrolein was performed. Chebuloside II, Sericoside, 24-deoxysericoside, arjunglucoside 1 and 23-galloylarjunolic acid 28-O-glucopyranosylester were identified by LC-MS. GT-TeMac™ has a SC 50 of 9.54 μg/mL and an ORAC value of 1130 µM Trolox equivalent per mg of GT-TeMac™. The administration of GT-TeMac™ protected against cognitive decline in AD by inhibiting cholinesterase metabolism, modulating oxidative stress parameters and protecting hippocampal areas. Additionally, GT-TeMac™ absorbed and eliminated ROS produced by hydrogen peroxide in SKNSH cells and restored cell viability reduced by acrolein. These findings suggest that the active ingredients in GT-TeMac™ are promising drug candidates for the treatment of cognitive disorders associated with oxidative stress in AD. • Five glycosyl-terpenoids from the GT-TeMac™ identified by LC-MS in this study. • GT-TeMac™ traps free radicals and displays a high Oxygen Radical Absorbance Capacity (ORAC). • GT-TeMac™ modulates cholinesterase (AchE and BuchE) metabolism in scopolamine-treated rats. • GT-TeMac™ reduces the level of TBARS and increases thiol proteins and catalase activity in the brain, while protecting hippocampal areas of scopolamine-treated rats. • GT-TeMac™ eliminates ROS produced by hydrogen peroxide in SK-N-SH cells.