Cinnamomum verum-derived O-methoxycinnamaldehyde prevents lipopolysaccharide-induced depressive-like behavior in mice via NFAT mRNA stability in T lymphocytes,Phytomedicine

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Cinnamomum verum-derived O-methoxycinnamaldehyde prevents lipopolysaccharide-induced depressive-like behavior in mice via NFAT mRNA stability in T lymphocytes
Phytomedicine ( IF 6.7 ) Pub Date : 2021-08-08 , DOI: 10.1016/j.phymed.2021.153703
Hye Jin Kim ₁ , Hyungjun Kim ₂ , Yujin Choi ₂ , Jun-Hwan Lee ₃ , Donghwan Kim ₄ , Sang Kook Lee ₅ , Ki-Sun Park ₂

Affiliation

Background

Depressive-like behaviors are related to inflammatory immune activation. Cinnamomum verum (CV) has anti-inflammatory effects, but the molecular mechanisms underlying the antidepressant effects after immunological activation still remain elusive.

Purpose

The aim of the present study was to investigate the effect of CV in improving depressive-like behavior and explore its underlying mechanism in T lymphocytes.

Methods

Mice were randomly divided into Control, LPS, LPS plus fluoxetine, LPS plus CV, and LPS plus MCA groups. Behavior was evaluated using forced swimming test (FST) and tail suspension test (TST). The experimental group mice were exposed to LPS to induce depressive-like behavior. Cell viability was measured upon treating splenic T lymphocytes and Jurkat T cells with CV. Cytokine activity was measured using ELISA and RT-qPCR. The components of CV were analyzed by HPLC. NFAT expression was evaluated by western blotting, immunofluorescence, and luciferase assay. To verify the half-life of NFAT mRNA, Jurkat cells were treated with actinomycin D for 1.5, 3, and 4.5 h.

Results

CV effectively prevents inflammation-induced depressive-like behaviors. CV dose-dependently decreased protein and mRNA levels of TNFα and IL-2. Inhibition of TNFα and IL-2 production involves an MCA-mediated decrease in NFAT mRNA level, rather than inhibition of nuclear translocation. This mechanism was independent of NFAT transcription inducer p38 MAPK; it can be attributed to the promotion of NFAT mRNA decay.

Conclusion

Overall, MCA might be an alternative or adjuvant to existing NFAT-targeting immunosuppressants for clinical prophylaxis or therapy in the context of inflammation-induced depressive disorder or other T-cell-associated inflammatory disorders.

中文翻译：

肉桂衍生的 O-甲氧基肉桂醛通过 T 淋巴细胞中的 NFAT mRNA 稳定性防止脂多糖诱导的小鼠抑郁样行为

背景

抑郁样行为与炎症免疫激活有关。肉桂(CV) 具有抗炎作用，但免疫激活后抗抑郁作用的分子机制仍然难以捉摸。

目的

本研究的目的是研究 CV 在改善抑郁样行为方面的作用，并探讨其在 T 淋巴细胞中的潜在机制。

方法

小鼠随机分为Control组、LPS组、LPS加氟西汀组、LPS加CV组、LPS加MCA组。使用强迫游泳测试（FST）和悬尾测试（TST）评估行为。实验组小鼠暴露于 LPS 以诱导抑郁样行为。在用 CV 处理脾 T 淋巴细胞和 Jurkat T 细胞后测量细胞活力。使用ELISA和RT-qPCR测量细胞因子活性。CV的组分通过HPLC分析。NFAT 表达通过蛋白质印迹、免疫荧光和荧光素酶测定进行评估。为了验证 NFAT mRNA 的半衰期，用放线菌素 D 处理 Jurkat 细胞 1.5、3 和 4.5 小时。

结果

CV 有效地防止炎症引起的抑郁样行为。CV 剂量依赖性地降低 TNFα 和 IL-2 的蛋白质和 mRNA 水平。TNFα 和 IL-2 产生的抑制涉及 MCA 介导的 NFAT mRNA 水平降低，而不是抑制核易位。这种机制独立于 NFAT 转录诱导剂 p38 MAPK；这可以归因于 NFAT mRNA 衰变的促进。