Xia Baomei, Tong Yue, Xia Changbo, Chen Chang, Shan Xin
Faculty of Rehabilitation Science, Nanjing Normal University of Special Education, Nanjing, China.
Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, United States.
Front Pharmacol. 2020 Oct 8;11:577062. doi: 10.3389/fphar.2020.577062. eCollection 2020.
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.
α-香附酮（Cy）是香附的一种主要活性化合物，具有多种药理活性。但Cy是否具有抗抑郁作用尚不清楚。在本研究中，我们使小鼠遭受慢性不可预测轻度应激（CUMS），并对其进行或不进行Cy干预。我们的结果表明，Cy在蔗糖偏好试验、悬尾试验和强迫游泳试验中显著改善了抑郁表型。同时，在小鼠海马中检测到SIRT3表达增加、活性氧生成减少以及NF-κB信号激活。给予Cy后，包括NLRP3、ASC、半胱天冬酶-1、白细胞介素-1β、白细胞介素-18和Gasdermin D-N在内的NLRP3炎性小体相关蛋白表达下调。Cy处理后，包括突触素-1和PSD-95在内的突触蛋白以及树突棘密度得到改善。此外，当与SIRT3抑制剂3-TYP共同给药时，Cy对CUMS小鼠的保护作用受到损害。综上所述，这些发现表明Cy具有治疗抑郁症的潜力，这种抗抑郁作用可能归因于SIRT3通过抑制NLRP3炎性小体刺激神经可塑性增强。
