Ambamba_2025_Biomed.Pharmacother_186_118010

BACKGROUND: 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. METHODS: 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. RESULTS: 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 microg/mL and an ORAC value of 1130 microM 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. CONCLUSION: 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.