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橙皮苷基于NLRP3炎症信号通路的抗抑郁作用及相关机制

The Anti-Depressive Effects of Hesperidin and the Relative Mechanisms Based on the NLRP3 Inflammatory Signaling Pathway.

作者信息

Xie Lulu, Gu Zhimin, Liu Haizhao, Jia Beitian, Wang Yiyang, Cao Min, Song Ruiwen, Zhang Zhaiyi, Bian Yuhong

机构信息

School of Intergrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

School of Management, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

出版信息

Front Pharmacol. 2020 Aug 14;11:1251. doi: 10.3389/fphar.2020.01251. eCollection 2020.

DOI:10.3389/fphar.2020.01251
PMID:32922291
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7456860/
Abstract

There is increasing evidence showing that inflammation is associated with depression in humans. Hesperidin, a natural bioflavonoid, has performed excellent effects on depression. The aim of this research was to investigate the therapeutic effect of hesperidin on chronic unpredictable mild stress (CUMS)-induced rats. The sucrose preference test (SPT), forced swimming test (FST), and open field test (OFT) were performed to measure the depression-related symptoms. The enzyme-linked immunosorbent assay (ELISA) was used to determine the concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the prefrontal cortex (PFC) of rats and cellular supernatant. PCR and Western blot were used to monitor the differences of NLRP3, caspase-1, ASC activation in the levels of genes and proteins in the PFC of rats and microglia. The activation of microglia was determined using immunofluorescence staining and flow cytometry assay. Our results show that hesperidin treatment significantly relieved depressive like behaviors in CUMS rats. In addition, hesperidin decreased the expression levels of IL-1β, IL-6, TNF-α, NLRP3, caspase-1, and ASC in the PFC and microglia. This study investigated that hesperidin treatment ameliorated CUMS-induced depression by suppressing microglia and inflammation.

摘要

越来越多的证据表明，炎症与人类抑郁症有关。橙皮苷是一种天然生物类黄酮，对抑郁症有显著疗效。本研究的目的是探讨橙皮苷对慢性不可预测轻度应激（CUMS）诱导的大鼠的治疗效果。采用蔗糖偏好试验（SPT）、强迫游泳试验（FST）和旷场试验（OFT）来测量与抑郁相关的症状。酶联免疫吸附测定（ELISA）用于测定大鼠前额叶皮质（PFC）和细胞上清液中白细胞介素（IL）-1β、IL-6和肿瘤坏死因子（TNF）-α的浓度。采用聚合酶链反应（PCR）和蛋白质印迹法（Western blot）监测大鼠PFC和小胶质细胞中NLRP3、半胱天冬酶-1（caspase-1）、凋亡相关斑点样蛋白（ASC）在基因和蛋白水平上的差异。采用免疫荧光染色和流式细胞术检测小胶质细胞的激活情况。我们的结果表明，橙皮苷治疗可显著缓解CUMS大鼠的抑郁样行为。此外，橙皮苷降低了PFC和小胶质细胞中IL-1β、IL-6、TNF-α、NLRP3、caspase-1和ASC的表达水平。本研究发现，橙皮苷治疗通过抑制小胶质细胞和炎症来改善CUMS诱导的抑郁症。

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