人参皂苷Re通过促进pink1介导的线粒体自噬抑制抑郁小鼠NLRP3炎性体激活

IF 6.2 1区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY
Shan Liu, Yue Zhang, Hao Zhou, Yating Ma, Fangzhou Huang, Tianyuan Lei, Qingbin Wang and Shangmin Yu*, 
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引用次数: 0

摘要

人参皂苷Re (Re)被证明对改善抑郁样行为有效。然而,Re的潜在抗抑郁机制仍未揭示。在这项研究中,我们研究了pink1介导的线粒体自噬和NLRP3炎症小体是否与慢性不可预测轻度应激(CUMS)小鼠和脂多糖(LPS)刺激的星形胶质细胞中Re的抗抑郁机制有关。通过RNA测序和生物信息学分析,我们发现了与Re相关的靶点和途径。通过pten诱导的推定激酶1 (PINK1)敲低,我们阐明了PINK1介导的线粒体自噬在Re抗抑郁机制中的作用。结果表明,Re改善了抑郁样行为,激活了PINK1介导的线粒体自噬,抑制了NLRP3炎症小体的激活。PINK1敲低可使Re的抗抑郁作用减弱。Re引起的线粒体自噬的促进和NLRP3炎性体活化的下降可被PINK1敲低逆转。综上所述,Re通过促进pink1介导的线粒体自噬来抑制NLRP3炎性体的激活,从而发挥其抗抑郁作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Ginsenoside Re Inhibits NLRP3 Inflammasome Activation in Depressive Mice by Promoting PINK1-Mediated Mitophagy

Ginsenoside Re Inhibits NLRP3 Inflammasome Activation in Depressive Mice by Promoting PINK1-Mediated Mitophagy

Ginsenoside Re (Re) was proved effective in improving depressive-like behaviors. However, the potential antidepressant mechanism of Re remains unrevealed. In this study, we investigated whether PINK1-mediated mitophagy and NLRP3 inflammasomes were linked to the antidepressant mechanism of Re in chronic unpredictable mild stress (CUMS) mice and lipopolysaccharide (LPS)-stimulated astrocytes. RNA sequencing and bioinformatics analyses were performed to discover the targets and pathways associated with Re. PTEN-induced putative kinase 1 (PINK1) knockdown was conducted to clarify the role of PINK1-mediated mitophagy in the antidepressant mechanism of Re. The outcomes showed that Re ameliorated depressive-like behaviors, activated PINK1-mediated mitophagy, and inhibited NLRP3 inflammasome activation. PINK1 knockdown attenuated the antidepressant effect of Re. The promotion of mitophagy and the decline of NLRP3 inflammasome activation caused by Re were reversed by PINK1 knockdown. In conclusion, Re inhibited NLRP3 inflammasome activation by promoting PINK1-mediated mitophagy to exert its antidepressant effect.

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来源期刊
Journal of Agricultural and Food Chemistry
Journal of Agricultural and Food Chemistry 农林科学-农业综合
CiteScore
9.90
自引率
8.20%
发文量
1375
审稿时长
2.3 months
期刊介绍: The Journal of Agricultural and Food Chemistry publishes high-quality, cutting edge original research representing complete studies and research advances dealing with the chemistry and biochemistry of agriculture and food. The Journal also encourages papers with chemistry and/or biochemistry as a major component combined with biological/sensory/nutritional/toxicological evaluation related to agriculture and/or food.
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