Abstract
Context Moringa oleifera Lam. (Moringaceae) and Ganoderma lucidum (Curtis) P. Karst. (Ganodermataceae) are two natural resources with established neuroprotective properties. However, whether their combination is safe and has neuroprotective effects against dementia remains unexplored.Objective This study aimed to investigate the phytochemical composition, toxicity profile, and neuroprotective activity of fermented M. oleifera and G. lucidum mixture (FMG) in scopolamine-induced dementia model rats.Methods FMG was produced by fermentation with Bacillus subtilis. A state of cognitive impairment was induced in rats via daily intraperitoneal administration of scopolamine (4 mg/kg) for 28 days. Following a two-week treatment period, cognitive function was assessed using the Y-maze. Postmortem analyses included biochemical assays to measure brain acetylcholinesterase (AChE) activity and oxidative stress markers, and histological examination of the hippocampus.Results LC-MS analysis revealed a rich phytochemical profile. The no-observed-adverse-effect level (NOAEL) was 200 mg/kg/day, while the lowest-observed-adverse-effect level (LOAEL) was 600 mg/kg/day. Treatment at the 200 mg/kg dose significantly reversed memory deficits, restoring spontaneous alternation from 29.1% in scopolamine-treated rats to 82.6% (p < 0.05). This behavioral recovery was correlated with a significant reduction in brain AChE activity, a normalization of lipid peroxidation (TBARS) levels, and the restoration of hippocampal neuronal architecture.Discussion and conclusions The restorative effects of FMG are mediated by a dual mechanism involving the enhancement of central cholinergic and antioxidant systems. These results suggest that FMG possesses neuroprotective and antioxidant properties and could be a promising candidate for the management of cognitive deficits.