Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway.
Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway.
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芒柄花素通过抑制 NLRP3 炎症小体信号通路改善硫酸葡聚糖钠诱导的急性结肠炎
DOI：
10.1155/2018/3048532
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发表时间：
2018
影响因子：
4.6
通讯作者：
Ding Y
中科院分区：
文献类型：
--
作者：
Wu D;Wu K;Zhu Q;Xiao W;Shan Q;Yan Z;Wu J;Deng B;Xue Y;Gong W;Lu G;Ding Y
芒柄花素是一种具有抗炎作用的黄酮类化合物。本研究旨在探讨芒柄花素对葡聚糖硫酸钠（DSS-）诱导的急性结肠炎的保护作用。小鼠腹腔注射刺芒柄花素后，结肠炎的病情严重程度呈剂量依赖性减轻，主要表现为结肠炎的临床症状减轻，结肠上皮细胞损伤减轻，结肠紧密连接蛋白（ZO-1、claudin-1和occludin）水平上调。同时，我们的研究发现芒柄花素对TNF-α诱导的结肠细胞急性损伤有明显的保护作用，具体表现为结肠紧密连接蛋白ZO-1、claudin-1和occludin的表达增加。此外，刺芒柄花素可降低NLRP 3通路蛋白（NLRP 3、ASC、IL-1β）的水平，NLRP 3特异性抑制剂MCC 950可减轻DSS诱导的小鼠急性结肠炎。此外，在给予MCC 950抑制NLRP 3炎性体活化的基础上，我们未能观察到芒柄花素对小鼠急性结肠炎的保护作用。总的来说，我们的研究首次证实了芒柄花素通过抑制NLRP 3炎性体通路激活对DSS诱导的急性结肠炎的保护作用。
Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1β) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.
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影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
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影响因子：
3.2
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
Pan Y;Li Y;Gao L;Tong Z;Ye B;Liu S;Li B;Chen Y;Yang Q;Meng L;Wang Y;Liu G;Lu G;Li W;Li J
通讯作者：
Li J