Suppression of iNOS and COX-2 expression by flavokawain A via blockade of NF-κB and AP-1 activation in RAW 264.7 macrophages
Suppression of iNOS and COX-2 expression by flavokawain A via blockade of NF-κB and AP-1 activation in RAW 264.7 macrophages
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DOI：
10.1016/j.fct.2013.05.031
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发表时间：
2013-08-01
影响因子：
4.3
通讯作者：
Park, Jinseu
中科院分区：
文献类型：
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作者：
Kwon, Dong-Joo;Ju, Sung Mi;Park, Jinseu
卡瓦胡椒黄素A是卡瓦胡椒提取物中查尔酮的主要成分，具有多种生物活性，如抗肿瘤活性。在这项研究中，我们研究了黄素卡瓦A对LPS诱导的促炎介质表达的抑制作用，以及在小鼠巨噬细胞中负责这些活动的分子机制。在LPS刺激的RAW 264.7细胞中，卡瓦胡椒素A显著抑制iNOS和考克斯-2的表达，以及随后的NO和PGE（2）的产生。卡瓦胡椒素A显著抑制LPS诱导的NF-κ B和AP-1信号通路的激活。另外，卡瓦胡椒素A抑制JNK和p38 MAPK的活化，而JNK和p38 MAPK是LPS刺激RAW 264.7细胞诱导型一氧化氮合酶（iNOS）和考克斯-2表达的重要因素。此外，卡瓦胡椒素A抑制LPS诱导的促炎细胞因子如TNF-α、IL-1 β和IL-6的表达。这些结果表明，黄素卡瓦菌素A可能通过阻断小鼠巨噬细胞中NF-κ B-AP-1-JNK/p38 MAPK信号通路来抑制LPS诱导的促炎介质的表达，从而发挥抗炎反应。(C)2013爱思唯尔有限公司保留所有权利。
Flavokawain A, a major constituent of chalcones derived from kava extracts, exerts various biological activities such as anti-tumor activities. In this study, we examined the suppressive effect of flavokawain A on LPS-induced expression of pro-inflammatory mediators and the molecular mechanisms responsible for these activities in the murine macrophages. Flavokawain A significantly suppressed expression of iNOS and COX-2, as well as the subsequent production of NO and PGE(2) in the LPS-stimulated RAW 264.7 cells. Flavokawain A significantly inhibited LPS-induced activation of NF-kappa B and AP-1 signaling pathways. In addition, flavokawain A inhibited activation of JNK and p38 MAPK which was responsible for expression of iNOS and COX-2 in the LPS-stimulated RAW 264.7 cells. Furthermore, flavokawain A suppressed LPS-induced expression of pro-inflammatory cytokines, such as TNF-alpha, IL-1 beta and IL-6. These results suggest that flavokawain A may exert anti-inflammatory responses by suppressing LPS-induced expression of pro-inflammatory mediators via blockage of NF-kappa B-AP-1-JNK/p38 MAPK signaling pathways in the murine macrophages. (C) 2013 Elsevier Ltd. All rights reserved.