Abstract
Nimesulide is an inhibitor of COX-2 with antioxidant and anti-inflammatory effects. However, few studies have explored the antidepressant mechanism of nimesulide. Here, we evaluated the therapeutic effects of nimesulide on CUMS rats. iTRAQ technology was used to identify the differentially expressed protein in the hippocampus between CUMS and nimesulide-treated rats to identify the possible molecular mechanism of its effects. We found that nimesulide had positive effects on depressive-like behaviors and inflammatory factors in depressed rats. Using proteomics technologies, we screened 16 differentially expressed proteins in CUMS-exposed rats after nimesulide treatment, 5 of which were related to inflammation. Overall, these results show that nimesulide might mediate its antidepressant effect on depressed rats through the inhibition of oxidative stress inflammatory response.
Highlights
Nimesulide is an inhibitor of COX-2 with antioxidant and anti-inflammatory effects
Compared with CUMS group, we found that nimesulide increased the horizontal and vertical movements (F3,52 = 21, p < 0.05; F3,52 = 13, p < 0.01; Fig. 1a–b)
We found that nimesulide significantly shortened immobility time compared with CUMS group (F3,44 = 8.3, p < 0.05; Fig. 1c)
Summary
Nimesulide is an inhibitor of COX-2 with antioxidant and anti-inflammatory effects. few studies have explored the antidepressant mechanism of nimesulide. We screened 16 differentially expressed proteins in CUMS-exposed rats after nimesulide treatment, 5 of which were related to inflammation Overall, these results show that nimesulide might mediate its antidepressant effect on depressed rats through the inhibition of oxidative stress inflammatory response. Clinical studies found that enhanced COX-2 expression in patients with neuropsychiatric diseases such as depression and Alzheimer’s disease[12,13,14] Consistent with these results, an animal model of depression in rats demonstrated that the upregulation of COX-2 may induce hyperactivity in inflammatory responses and lead to depression-like behavior[15]. In people with major depression, a randomized, double-blind study found compared reboxetine plus celecoxib with reboxetine plus placebo a significant therapeutic effect of celecoxib[17] These results point out that a strong correlation between COX-2 and depression. We used iTRAQ to screen target proteins regulated by nimesulide in the hippocampus of CUMS rats, to provide insight into the pathogenesis of depression and the role of nimesulide in depression
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