Evodiamine Attenuates Experimental Colitis Injury Via Activating Autophagy and Inhibiting NLRP3 Inflammasome Assembly.

Evodiamine Attenuates Experimental Colitis Injury Via Activating Autophagy and Inhibiting NLRP3 Inflammasome Assembly.
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吴茱萸碱通过激活自噬和抑制 NLRP3 炎症小体组装减轻实验性结肠炎损伤。

DOI:
10.3389/fphar.2020.573870
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发表时间:
2020
影响因子:
5.6
通讯作者:
Du R
Du R
中科院分区:
医学2区
文献类型:
--
作者:
Ding W;Ding Z;Wang Y;Zhu Y;Gao Q;Cao W;Du R

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自噬和NLRP3炎症体与结肠炎的发生密切相关。针对NLRP3炎症小体和自噬治疗结肠炎的药物缺乏,它们是迫切需要的。在本实验中,我们观察了吴茱萸碱对葡聚糖硫酸钠诱导的实验性结肠炎的影响,以及吴茱萸碱对自噬和NLRP3炎症体的影响。我们的数据表明吴茱萸碱可以改善结肠炎,包括改善小鼠的体重、结肠长度、组织病理学评分和疾病活动性指数。我们还观察到吴茱萸碱通过抑制THP-1巨噬细胞中凋亡相关的SPECK样蛋白寡聚和caspase-1活性来抑制NLRP3炎症体的形成。我们的结果表明吴茱萸碱通过诱导自噬体介导炎性小体的降解和抑制NF-κB途径来抑制NLRP3型炎性小体的激活,从而协同作用于吴茱萸碱对结肠炎的作用。提示吴茱萸碱在炎症性肠病治疗中具有潜在的应用前景。
Autophagy and NLRP3 inflammasome were associated with the process of colitis. Drugs targeting NLRP3 inflammasome and autophagy to treat colitis are absent, and they are urgently required. Herein, we examine the effect of evodiamine, extracted from the fruit of Evodiae Fructus, on experimental colitis induced by dextran sulfate sodium and exposit whether evodiamine effects on autophagy and NLRP3 inflammasome. Our data indicated that colitis was ameliorated by evodiamine, including the improvement of mice body weight, colon length, histopathologic score, and the disease activity index. We also observed that evodiamine restrained the formation of the NLRP3 inflammasome by inhibiting the apoptosis-associated speck-like protein oligomerization and caspase-1 activity in THP-1 macrophages. Our results demonstrated evodiamine inhibit NLRP3 inflammasome activation via the induction of autophagosome-mediated degradation of inflammasome and the inhibition of NFκB pathway, which synergistically contribute to the effect of evodiamine in colitis. It indicates the potential use of evodiamine in inflammatory bowel diseases treatment.
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