Abstract
Thymoquinone (TMQ), one of the main components active of Nigella sativa, shows very useful biomedical properties. Evidence suggests that cholinergic dysfunction and oxidative stress play role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). In the present study, we investigated the anti-amnestic effect of TMQ in scopolamine-induced animal model of AD. Wistar rats were randomly divided into four groups; Sham(SH), TMQ-treated(TMQ), scopolamine-treated(SCO) and scopolamine+TMQ-treated(SCO_TMQ) groups. TMQ (20 mg/kg) prepared in corn oil was administered intraperitoneally (i.p.) 1-h before experiments. Scopolamine (1 mg/kg) dissolved in 0.9% physiological saline was administered intraperitoneally (i.p.). We recorded mismatch negativity (MMN) response as an electrophysiological correlate of echoic memory. Object location memory (OLM) and Y-maze alternation tests were carried out to assess spatial memory. Then, the brain homogenates content of thiobarbituric-acid-reactive-substances (TBARS), 4-Hydroxy-2-nonenal (4-HNE) and acetylcholine (ACh)/acetylcholine (AChE) activity were biochemically determined. In the scopolamine-treated rats, TMQ was found to significantly improve the discrimination and spontaneous alteration levels in the OLM and Y-maze tests, respectively. Furthermore, TMQ significantly mitigated the scopolamine-induced attenuation of MMN and related theta responses. Moreover, scopolamine treatment increased TBARS/4-HNE level and decreased ACh level in the brain, and TMQ was able to significantly prevent these effects. AChE activity was increased in the SCO group; this effect was significantly attenuated by TMQ. TMQ diminished the lipid peroxidation and cholinergic dysfunction in the scopolamine-induced AD rat model which all reflected in improving the MMN/theta response and spatial memory. This may implement TMQ as an adjuvant therapeutic strategy in ameliorating AD.
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