Cardamonin inhibits COX and iNOS expression via inhibition of p65NF-κB nuclear translocation and Iκ-B phosphorylation in RAW 264.7 macrophage cells
Cardamonin inhibits COX and iNOS expression via inhibition of p65NF-κB nuclear translocation and Iκ-B phosphorylation in RAW 264.7 macrophage cells
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DOI：
10.1016/j.molimm.2006.04.025
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发表时间：
2007-02-01
影响因子：
3.6
通讯作者：
Khozirah, S.
中科院分区：
文献类型：
--
作者：
Israf, D. A.;Khaizurin, T. A.;Khozirah, S.
小豆蔻素是一种从当地植物Alpinia rafflesiana的果实中分离出来的查耳酮，在炎症的细胞模型中表现出抗炎活性。在本报告中，我们评估了小豆蔻素抑制NO和PGE（2）合成、iNOS和考克斯-2表达和酶活性以及NF-κ B途径中的关键分子的能力，以确定其分子靶点。小豆蔻素抑制干扰素-γ（IFN-γ）和脂多糖（LPS）诱导的RAW 264.7细胞中NO和PGE 2的产生。这种抑制被证明是由诱导酶iNOS和考克斯-2的剂量依赖性下调引起的，对iNOS或考克斯-2酶活性没有直接影响。随后，我们确定诱导酶表达的抑制是由于I-κ B α磷酸化和降解的剂量依赖性抑制，这导致p65 NF-κ B核转位的减少。我们的结论是，豆蔻明是一个潜在的抗炎药铅的目标NF-κ B通路。(c)2006爱思唯尔有限公司保留所有权利。
Cardamonin, a chalcone isolated from the fruits of a local plant Alpinia rafflesiana, has demonstrated anti-inflammatory activity in cellular models of inflammation. In this report, we evaluated the ability of cardamonin to suppress both NO and PGE(2) synthesis, iNOS and COX-2 expression and enzymatic activity, and key molecules in the NF-kappa B pathway in order to determine its molecular target. Cardamonin suppressed the production of NO and PGE2 in interferon-gamma (IFN-gamma)- and lipopolysaccharide (LPS)-induced RAW 264.7 cells. This inhibition was demonstrated to be caused by a dose-dependent down-regulation of both inducible enzymes, iNOS and COX-2, without direct effect upon iNOS or COX-2 enzyme activity. Subsequently we determined that the inhibition of inducible enzyme expression was due to a dose-dependent inhibition of phosphorylation and degradation Of I-kappa B alpha, which resulted in a reduction of p65NF-kappa B nuclear translocation. We conclude that cardamonin is a potential anti-inflammatory drug lead that targets the NF-kappa B pathway. (c) 2006 Elsevier Ltd. All rights reserved.