Investigating the molecular mechanisms underlying the neuroprotective potential of ellagic acid in scopolamine-induced learning and memory dysfunction
TL;DR
EA attenuates scopolamine-induced memory deficits, accompanied by improvements in oxidative stress markers, neuroinflammatory gene expression, and cholinergic parameters, which suggest a potential neuroprotective role of EA.
Abstract
Background and purpose: Scopolamine-induced memory impairment is widely used as an experimental model of cognitive dysfunction. Natural compounds with antioxidant and anti-inflammatory properties, such as ellagic acid (EA), have shown neuroprotective potential; however, their effects on cholinergic signaling and neurotrophic factors remain underexplored. This study aimed to investigate the effects of EA on cognitive performance, oxidative stress, neuroinflammation, and cholinergic markers in scopolamine-treated rats. Experimental approach: Fifty adult male Wistar rats were divided into control, scopolamine (Scop, 2 mg/kg, i.p.), Scop + EA (25 or 50 mg/kg, orally), and Scop + donepezil (2 mg/kg, orally) groups. Cognitive functions were assessed using the MWM and PA tests. Biochemical assays measured hippocampal and cortical levels of MDA, thiols, SOD, CAT, and AChE activity. In addition, hippocampal BDNF concentration and mRNA expression of pro-inflammatory cytokines, AChE, and CHRM1 were quantified. Results/Findings: Scopolamine administration significantly impaired learning and memory in both MWM and PA tests, increased oxidative stress markers, reduced antioxidant enzyme activities, decreased hippocampal BDNF levels, and upregulated pro-inflammatory cytokines, AChE mRNA levels, and decreased CHRM1 mRNA expression. EA treatment (particularly at 50 mg/kg) significantly improved behavioral performance, restored antioxidant balance, enhanced BDNF expression, reduced AChE activity, and downregulated cytokine and AChE mRNA expression, while increasing CHRM1 mRNA expression, with effects comparable to those of donepezil. Conclusion and implications: EA attenuates scopolamine-induced memory deficits, accompanied by improvements in oxidative stress markers, neuroinflammatory gene expression, and cholinergic parameters. These findings suggest a potential neuroprotective role of EA; however, the underlying mechanisms remain speculative.