Anti-Depressant-Like Effect of Sinomenine on Chronic Unpredictable Mild Stress-Induced Depression in a Mouse Model.
Anti-Depressant-Like Effect of Sinomenine on Chronic Unpredictable Mild Stress-Induced Depression in a Mouse Model.
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DOI：
10.12659/msm.908422
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发表时间：
2018-10-26
期刊：
影响因子：
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通讯作者：
Shen Z
中科院分区：
文献类型：
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作者：
Liu S;Xu S;Wang Z;Guo Y;Pan W;Shen Z
青藤碱是中草药青藤碱的提取物，具有免疫抑制、抗炎等多种药理作用。本研究旨在观察SIN对慢性不可预测轻度应激(CUMS)所致抑郁小鼠模型是否具有抗抑郁作用，并探讨其可能的分子机制。建立小鼠抑郁模型，给予不同浓度的SIN(30、100、300 mg/kg)治疗。然后进行行为测试，包括蔗糖偏好试验(SPT)、强迫游泳试验(FST)和尾部悬吊试验(TST)。采用双抗体夹心法检测小鼠海马区去甲肾上腺素(NE)、5-羟色胺(5-羟色胺)和促炎性细胞因子(IL-1β[IL-1β]IL-6[IL-6]和肿瘤坏死因子α[TNF-α])水平。用Western印迹和/或qRT-PCR检测p-p38、p-p65、NLRP3、Asc和caspase-1的表达。结果表明，SIN可显著减轻CUMS诱导的抑郁样行为。与模型组比较，SIN组小鼠对蔗糖的偏好性明显增强，强迫游泳和悬尾实验中的不动时间明显缩短。此外，SIN还可降低由CUMS引起的小鼠海马区NE和5-羟色胺含量的降低。SIN可降低CMS诱导的小鼠海马区IL-1β、IL-6和肿瘤坏死因子-α水平的升高。此外，SIN还可抑制CMS诱导的p38MAPK-NF-κB通路的激活和核苷酸结合及寡聚化结构域样受体家族3(NLRP3)的炎性小体。综上所述，我们的结果表明，SIN对慢性不可预测的轻度应激诱导的小鼠抑郁具有抗抑郁作用。
Sinomenine (SIN) is an extract of the Chinese medicinal herb Sinomenium acutum; it has various pharmacological properties, including immunosuppression and anti-inflammation. The present study aimed to investigate whether SIN has an anti-depressant-like effect in a mouse model of depression induced by chronic unpredictable mild stress (CUMS), and to explore the underlying molecular mechanisms. A mouse model of depression was established and treated with different concentrations of SIN (30, 100, or 300 mg/kg). Then, behavioral tests, including sucrose preference test (SPT), forced swimming test (FST), and the tail suspension test (TST), were performed. The levels of norepinephrine (NE), 5-hydroxytryptamine (5-HT), and proinflammatory cytokines (interleukin-1β [IL-1β] interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]) in the hippocampus of mice were detected by ELISA assay. The levels of p-p38, p-p65, NLRP3, ASC, and caspase-1 were measured by Western blot or/and qRT-PCR. The results showed that SIN significantly relieved CUMSinduced depressive-like behaviors. Compared with the model mice, SIN treatment significantly increased the sucrose preference of the mice, and the immobility time in the forced swimming and the tail suspension test were shortened. In addition, SIN decreased CUMS-induced reduction in the concentrations of NE and 5-HT in the hippocampus of mice. SIN reduced CUMS-induced increases in the levels of IL-1β, IL-6, and TNF-α in the hippocampus of mice. Furthermore, activation of the p38MAPK-NF-κB pathway and the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome induced by CUMS were inhibited by SIN treatment. In conclusion, our results indicate the antidepressantlike effects of SIN on chronic unpredictable mild stress-induced depression in a mouse model.