α-Cyperone Confers Antidepressant-Like Effects in Mice via Neuroplasticity Enhancement by SIRT3/ROS Mediated NLRP3 Inflammasome Deactivation.

α-Cyperone Confers Antidepressant-Like Effects in Mice via Neuroplasticity Enhancement by SIRT3/ROS Mediated NLRP3 Inflammasome Deactivation.
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α-Cyperone 通过 SIRT3/ROS 介导的 NLRP3 炎性体失活增强神经可塑性,赋予小鼠抗抑郁样作用

DOI:
10.3389/fphar.2020.577062
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发表时间:
2020
影响因子:
5.6
通讯作者:
Shan X
Shan X
中科院分区:
医学2区
文献类型:
--
作者:
Xia B;Tong Y;Xia C;Chen C;Shan X

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α-赛柏酮(cyperone, Cy)是圆形赛柏的主要活性化合物,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,我们将小鼠置于慢性不可预测轻度应激(CUMS)下,在有或没有Cy干预的情况下,我们的研究结果表明,Cy显著改善了蔗糖偏好测试、悬尾测试和强迫游泳测试中的抑郁表型。同时,小鼠海马SIRT3表达升高,ROS生成减少,NF-κB信号激活。NLRP3炎性小体相关蛋白包括NLRP3、ASC、Caspase-1、IL-1β、IL-18和GSDMD-N在Cy给药后下调。Cy处理后突触蛋白Synapsin-1和PSD-95及树突棘密度均有改善。此外,Cy在CUMS小鼠中的保护作用与SIRT3抑制剂3-TYP共同给药时受到损害。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炎性体刺激神经可塑性增强。
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.
DOI: 10.1159/000480367
发表时间: 2017-01-01
影响因子: --
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DOI: 10.12659/msm.908529
发表时间: 2018-08-30
期刊: Medical science monitor : international medical journal of experimental and clinical research
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