Thymoquinone protects against cerebral small vessel disease: Role of antioxidant and anti-inflammatory activities.

Cerebral small vessel disease (CSVD) is a leading cause of progressive decline of cognition and a major risk factor for stroke. Thymoquinone (TQ) is the major biological component of Nigella sativa (N. sativa) and its extracts. We explored the possible protective effect of TQ against CSVD in strokeprone spontaneously hypertensive SHRsp rats. Morris water maze and novel object recognition tests were conducted to evaluate memory and cognitive function. mRNA expression of inflammatory factors were determined and oxidative stress was evaluated. We showed that TQ markedly decreased the level of systolic blood pressure in SHRsp rats. TQ reduced the escape latency time and the time spent in the target quadrant in the Morris water maze test in SHRsp rats. TQ also decreased the time spent with the novel object in SHRsp rats in both short- and long-term memory tests. TQ markedly increased the capacity to distinguish between familiar objects and novel objects in the SHRsp rats in the short- and long-term memory tests. The mRNA expression of IL-1β, IL-6, monocyte chemoattractant protein-1 and cyclooxygenase-2 in the brain of SHRsp rats was remarkably decreased by TQ, indicating the reduction of inflammation. Moreover, TQ increased the activities of superoxide dismutase and catalase, decreased the malondialdehyde level and increased glutathione level in the brain of SHRsp rats, indicating the attenuation of oxidative stress. In summary, we found that TQ could effectively attenuate the blood pressure and the injury of memory and cognition under the condition of CSVD. The anti-inflammatory and antioxidant activities of TQ may be responsible for its protective effect. We demonstrate that TQ is a novel candidate for the treatment of CSVD and its neurological outcome.