Abstract
α-Cyperone (Cy) is a major active compound of Cyperus rotundus that has various pharmacological activities. But whether Cy possesses antidepressant effect is unknown. In this study, we exposed mice to chronic unpredictable mild stress (CUMS) with or without intervention with Cy. Our results showed that Cy significantly improved the depressive phenotypes in sucrose preference test, tail suspension test and forced swimming test. Meanwhile, increased SIRT3 expression, reduced ROS production and activated NF-κB signal were detected in the hippocampus of mice. NLRP3 inflammasome related proteins including NLRP3, ASC, Caspase-1, IL-1β, IL-18 and GSDMD-N were downregulated after Cy administration. Synaptic proteins including Synapsin-1 and PSD-95 and dendritic spine density were improved after Cy treatment. Moreover, the protective effects of Cy in CUMS mice were compromised when co-administrated with SIRT3 inhibitor 3-TYP. Taken together, these findings suggested that Cy has therapeutic potential for treating depression and that this antidepressant effect may be attributed to SIRT3 stimulated neuroplasticity enhancement by suppressing NLRP3 inflammasome.
Highlights
Depression is a psychiatric disorder which affects more than one-fifth of the global population (Wang et al, 2019)
The protective effects of Cy in chronic unpredictable mild stress (CUMS) mice were compromised when co-administrated with SIRT3 inhibitor 3-TYP. These findings suggested that Cy has therapeutic potential for treating depression and that this antidepressant effect may be attributed to SIRT3 stimulated neuroplasticity enhancement by suppressing NLRP3 inflammasome
Treatment with Cy (5 mg/kg, 10 mg/kg in TST; 10 mg/kg in FST) and Flu reduced the immobile time in CUMS mice in both tests, suggesting that Cy and Flu ameliorated the depression-like behaviors in mice induced by CUMS
Summary
Depression is a psychiatric disorder which affects more than one-fifth of the global population (Wang et al, 2019) It causes considerable burden on individuals and society with its high morbidity, recurrence, and mortality (Feng et al, 2019). A number of antidepressants including mainstream antidepressants SSRIs are used in the clinical treatment of depression. Disadvantages such as delayed onset time, inadequate response rate, and side effects such. Therapies exerted rapid and significant antidepressant effects via dendritic spine remodeling and neuroplasticity related protein enhancement (McAvoy et al, 2015; Menard et al, 2016)
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