Abstract
Background and Objective: Exposure to chronic stress is harmful to vital organs such as the brain and the heart. The potential inhibitory effects of the polyphenolic compound quercetin on Chronic Unpredictable Stress (CUS)-induced depression and biomarkers of brain injury associated with the inhibition of Nitrosative Stress (iNOS) and the apoptotic axis p53-Bax-caspase-3 has not been investigated before. Materials and Methods: Rats were either exposed to a variety of unpredictable stressors daily before being sacrificed after 3 weeks or were treated for 3 weeks with quercetin (50 mg kg(-1) b.wt./day). Animals were then culled and brain tissues were harvested. Results: CUS significantly (p<0.05) induced iNOS, MDA, p53, Bax and caspase-3, which were significantly inhibited by quercetin. Whereas, quercetin significantly increased brain tissue levels of SOD and Bcl-2. In addition, CUS caused a significant increase in animal immobility and a decrease in climbing ability and sucrose consumption, which were reverted by quercetin. Furthermore, a significant (p<0.0001) correlation between either cerebral cortex brain injury and biomarkers of apoptosis and survival, p53 and Bcl-2, or between p53 and Bcl-2 and biomarkers of nitrosative stress and depression were observed. Conclusion: Quercetin protects against CUS-induced cerebral cortex injury and depression, which is associated with the inhibition of the p53-Bax-caspase-3 axis and biomarkers of nitrosative and oxidative stress.