Oroxylin A inhibits colitis by inactivating NLRP3 inflammasome.
Oroxylin A inhibits colitis by inactivating NLRP3 inflammasome.
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Oroxylin A 通过灭活 NLRP3 炎症小体抑制结肠炎
DOI：
10.18632/oncotarget.19440
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发表时间：
2017-08-29
期刊：
影响因子：
--
通讯作者：
Hu R
中科院分区：
文献类型：
--
作者：
Zhou W;Liu X;Zhang X;Tang J;Li Z;Wang Q;Hu R
NLRP3炎性小体是治疗炎症性肠病（IBD）的新靶点。本研究旨在探讨生物活性类黄酮- oroxylin a通过靶向NLRP3炎性体治疗葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的抗炎作用。在本研究中，我们发现oroxylin A能减轻小鼠实验性结肠炎，包括体重减轻、结肠长度缩短和炎症细胞浸润。oroxylin A也显著降低结肠组织中IL-1β、IL-6和TNF-α的产生，oroxylin A显著降低肠黏膜组织中NLRP3的表达。此外，NLRP3-/-小鼠对dss诱导的急性结肠炎有明显的保护作用，oroxylin A治疗对NLRP3-/-小鼠的炎症没有减轻作用。进一步研究发现，在THP-Ms和BMDMs中，oroxylin A均能剂量依赖性地抑制NLRP3炎症小体的激活，从而降低caspase-1的裂解和IL-1β的分泌。oroxylin A的这种抑制作用是由于抑制了巨噬细胞中NLRP3蛋白的表达和炎性体的形成。此外，oroxylin A对NLRP3蛋白表达的降低依赖于对NF-κB p65表达和核易位的抑制。此外，oroxylin A直接抑制ASC斑点的形成和炎症小体的组装，从而抑制NLRP3炎症小体的激活。我们的研究结果表明，oroxylin A抑制NLRP3炎性体的激活，可能用于治疗IBD。
NLRP3 inflammasome is a novel therapeutic target for inflammatory bowel disease (IBD). The aim of this study was to investigate the anti-inflammatory effect of a bioactive flavonoid—oroxylin A on the treatment of dextran sulfate sodium (DSS)-induced murine colitis via targeting NLRP3 inflammasome. In this study, we found that oroxylin A attenuated experimental colitis in mice, including loss of body weights, shortening of the colon lengths and infiltration of inflammatory cells. The production of IL-1β, IL-6 and TNF-α in colon was also markedly reduced by oroxylin A. Moreover, oroxylin A significantly decreased the expression of NLRP3 in intestinal mucosal tissue. In addition, NLRP3-/- mice were observably protected from DSS-induced acute colitis, and oroxylin A treatment had no effects on attenuating inflammation in NLRP3-/- mice. Further study found that the activation of NLRP3 inflammasome was dose-dependently inhibited by oroxylin A in both THP-Ms and BMDMs, followed by decrease in the cleavage of caspase-1 and secretion of IL-1β. This inhibitory effect of oroxylin A was due to restraint of the NLRP3 protein expression and the inflammasome formation in macrophages. Furthermore, the reduction of NLRP3 protein expression by oroxylin A was dependent on the inhibition of NF-κB p65 expression and nuclear translocation. Besides, oroxylin A directly suppressed the ASC speck formation and the inflammasome assembly which in turn restrained the activation of NLRP3 inflammasome. Our findings demonstrated that oroxylin A inhibited NLRP3 inflammasome activation and could potentially be used for the treatment of IBD.
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影响因子：
3.9
作者：
Ponder A;Long MD
通讯作者：
Long MD
影响因子：
4.4
作者：
Lalor, Stephen J.;Dungan, Lara S.;Mills, Kingston H. G.
通讯作者：
Mills, Kingston H. G.
DOI：
10.1007/s00281-005-0208-4
发表时间：
2005-06-01
期刊：
SPRINGER SEMINARS IN IMMUNOPATHOLOGY
影响因子：
--
作者：
Lorenz, RG;McCracken, VJ;Elson, CO
通讯作者：
Elson, CO
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影响因子：
4.9
作者：
Yang, Xi;Zhang, Fengyi;Hu, Rong
通讯作者：
Hu, Rong
影响因子：
24.5
作者：
Bauer, Christian;Duewell, Peter;Schnurr, Max
通讯作者：
Schnurr, Max