Ginsenoside Rg1 ameliorates chronic social defeat stress-induced depressive-like behaviors and hippocampal neuroinflammation
Ginsenoside Rg1 ameliorates chronic social defeat stress-induced depressive-like behaviors and hippocampal neuroinflammation
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DOI：
10.1016/j.lfs.2020.117669
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发表时间：
2020-07-01
期刊：
影响因子：
6.1
通讯作者：
Liu, Xin-min
中科院分区：
文献类型：
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作者：
Jiang, Ning;Lv, Jingwei;Liu, Xin-min
慢性社会挫败压力（CSDS）是一种与行为学相关的心理社会压力动物模型，已广泛应用于抑郁症研究。人参皂苷Rg1（Rg1）是人参的主要活性成分，具有低毒和神经保护作用。本研究旨在探讨Rg1对CSDS小鼠的抗抑郁作用并探讨其分子机制。我们发现，通过社交互动测试和蔗糖偏好测试、悬尾测试和强迫游泳测试测量，Rg1（例如20或40 mg/kg）给药显着减轻了4周CSDS暴露引起的抑郁样行为。此外，Rgl治疗抑制CSDS诱导的IL-6、TNF-α和IL-1β的产生，降低iNOS、COX2以及caspase-9和-3的表达，并抑制海马中的小胶质细胞活化(Iba1)。研究发现 Rg1 显着下调 p-JNK1/2 和 p-P38 MAPK 水平，上调 p-ERK1/2 水平并抑制海马中磷酸化 NF-κ B 的表达。同时，Rg1 调节 SIRT1 并降低海马中乙酰化 p65 (ac-p65) 的水平。此外，Rg1 治疗可逆转 CSDS 小鼠成年海马神经发生的减少。总之，我们的研究结果表明，Rg1 部分通过下调海马神经炎症和上调成年海马神经发生来预防 CSDS 暴露小鼠的抑郁样行为，并且这些变化可能是通过增加抗炎作用以及抑制促炎细胞因子和神经毒性介质表达和小胶质细胞激活而发生的，这部分是通过 MAPK 和 SIRT1 信号通路的调节介导的，并导致 NF-κa 的抑制B 转录活性。
Chronic social defeat stress (CSDS) is an ethologically relevant psychosocial stress animal model and has been widely used in depression studies. Ginsenoside Rg1 (Rg1) is the major active ingredients of ginseng with low toxicity and neuroprotective effects. The present study aims to investigate the antidepressant effects of Rg1 in CSDS mice and explore its molecular mechanism. We found that Rg1 (20 or 40 mg/kg, i.g.) administration significantly alleviated depressive-like behaviors caused by 4-week CSDS exposure, as measured by social interaction test and sucrose preference test, tail suspension test and forced swim test. Additionally, Rgl treatment inhibited CSDS-induced production of IL-6, TNF-alpha and IL-1 beta, decreased the expression of iNOS, COX2, and caspase-9 and -3, and inhibited microglial activation (Iba1) in the hippocampus. Rg1 was found to significantly downregulate p-JNK1/2 and p-P38 MAPK levels, upregulate p-ERK1/2 levels and inhibit the expression of phosphorylated NF-kappa B in the hippocampus. Meanwhile, Rg1 regulated SIRT1 and decreased the levels of acetylated p65 (ac-p65) in the hippocampus. Moreover, the reduction in adult hippocampal neurogenesis in CSDS mice was reversed by Rg1 treatment. In conclusion, our findings suggest that Rg1 prevents depressive-like behavior in CSDS-exposed mice, partially through the downregulation of hippocampal neuroinflammation and the upregulation of adult hippocampal neurogenesis and that these changes presumably occur through increased anti-inflammatory effects and the inhibition of proinflammatory cytokine and neurotoxic mediator expression and microglial activation, which is partly mediated by the regulation of the MAPK and SIRT1 signaling pathways and results in the inhibition of NF-kappa B transcriptional activity.