College of Medicine, Jiaxing University, Jiaxing, Zhejiang, China (mainland).
Med Sci Monit. 2018 Oct 26;24:7646-7653. doi: 10.12659/MSM.908422.
BACKGROUND 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. MATERIAL AND METHODS 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. RESULTS 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. CONCLUSIONS In conclusion, our results indicate the antidepressantlike effects of SIN on chronic unpredictable mild stress-induced depression in a mouse model.
青藤碱（SIN）是中国草药青风藤的提取物，具有多种药理作用，包括免疫抑制和抗炎作用。本研究旨在探讨青藤碱是否对慢性不可预测轻度应激（CUMS）诱导的抑郁小鼠模型具有抗抑郁作用，并探讨其潜在的分子机制。
建立抑郁小鼠模型，用不同浓度的青藤碱（30、100 或 300mg/kg）进行治疗。然后进行行为测试，包括糖水偏好测试（SPT）、强迫游泳测试（FST）和悬尾测试（TST）。通过 ELISA 检测小鼠海马组织中去甲肾上腺素（NE）、5-羟色胺（5-HT）和促炎细胞因子（白细胞介素-1β[IL-1β]、白细胞介素-6[IL-6]和肿瘤坏死因子-α[TNF-α]）的水平。通过 Western blot 或/和 qRT-PCR 检测 p-p38、p-p65、NLRP3、ASC 和 caspase-1 的水平。
结果表明，SIN 可显著缓解 CUMS 诱导的抑郁样行为。与模型组相比，SIN 治疗显著增加了小鼠的糖水偏好，缩短了强迫游泳和悬尾试验中的不动时间。此外，SIN 降低了 CUMS 诱导的小鼠海马组织中 NE 和 5-HT 浓度的降低。SIN 降低了 CUMS 诱导的小鼠海马组织中 IL-1β、IL-6 和 TNF-α 水平的升高。此外，SIN 抑制了 CUMS 诱导的 p38MAPK-NF-κB 通路和核苷酸结合寡聚化结构域样受体家族 pyrin 结构域包含 3（NLRP3）炎症小体的激活。
综上所述，我们的研究结果表明，SIN 对慢性不可预测轻度应激诱导的抑郁模型具有抗抑郁作用。
