Nigella sativa and thymoquinone attenuate oxidative stress and cognitive impairment following cerebral hypoperfusion in rats

Nigella sativa, a plant widely used in traditional medicine, possesses anti-inflammatory, antioxidant and neuroprotective properties. In the present study, we investigated the effect of hydroalcoholic extract of N. sativa seeds (NSE) and its active constituent, thymoquinone (TQ), on learning and memory deficits, hippocampal acetylcholine esterase (AChE) activity, and markers of redox status, mainly lipid peroxidation and superoxide dismutase (SOD) activity following cerebral hypoperfusion in rats. Cerebral hypoperfusion was induced by permanent occlusion of bilateral common carotid arteries (2VO). Male Wistar rats were administered either a vehicle (sham group: 10 ml/kg/day, ip), NSE (100, 200, and 400 mg/kg/day, ip), TQ (10, 20, and 40 mg/kg/day, ip), or donepezil (5 mg/kg/day, ip) for 10 days (three days before and seven days after ligation). Spatial learning and memory deficits were investigated using the Morris water maze (MWM) task. 2VO produced significant learning and memory deficits as evidenced by increased latency time to reach the hidden platform, increased swimming time, and decreased time spent in the target quadrant in the probe trial in the MWM task. There was also a significant increase in the lipid peroxidation level and AChE activity, and a significant decrease in SOD activity in the hippocampal portion of hypoperfused rats, as compared with the sham group. Treatment with NSE (400 mg/kg/day; p < 0.001) and TQ (40 mg/kg/day; p < 0.001), as well as donepezil significantly prevented learning and memory impairments and alleviated changes in the hippocampal lipid peroxide level and SOD and AChE activities in this model. In conclusion, our data suggest that N. sativa and thymoquinone have a beneficial role in cerebrovascular insufficiency states and dementia.