Wogonin but not Nor-wogonin inhibits lipopolysaccharide and lipoteichoic acid-induced iNOS gene expression and NO production in macrophages
Wogonin but not Nor-wogonin inhibits lipopolysaccharide and lipoteichoic acid-induced iNOS gene expression and NO production in macrophages
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DOI：
10.1016/j.intimp.2007.04.001
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发表时间：
2007-08-01
影响因子：
5.6
通讯作者：
Chen, Yen-Chou
中科院分区：
文献类型：
--
作者：
Huang, Guam-Cheng;Chow, Jyh-Ming;Chen, Yen-Chou
我们先前的研究表明，汉黄素能有效地抑制脂多糖(LPS)诱导的诱导型一氧化氮合酶(INOS)基因表达和一氧化氮的产生。在本研究中，我们发现去甲汉黄素(N-Wog；5，7，8-三羟基黄酮)是Wog的结构类似物，在C8位有羟基取代，对内毒素或脂磷壁酸(LTA)诱导的巨噬细胞诱导型一氧化氮合酶基因表达和一氧化氮(NO)产生有不同的影响。Wog，而不是N-Wog，通过抑制iNOS基因在蛋白和mRNA上的表达而显著抑制内毒素或LTA诱导的NO产生，而不影响NO供体硝普钠诱导的NO产生、NOS酶活性和细胞存活率。在脂多糖和LTA处理的RAW264.7细胞中，通过磷酸化诱导JNKs(而不是ERKs)的激活和c-jun(而不是c-Fos)蛋白表达的增加涉及到这些事件，这些事件被Wog阻止，但N-Wog不能。此外，5，7-二羟基黄酮，而不是5-羟基黄酮、7-羟基黄酮、5-OH-7-OCH3黄酮能显著抑制内毒素诱导的iNOS蛋白表达和NO的产生，且7，8-diOCH(3)黄酮比7-OCH3-8-OH黄酮有更有效的抑制内毒素诱导的NO产生和iNOS蛋白表达的作用。这些数据表明，C5和C7的OHS对于NO抑制类黄酮是必不可少的，C8的OCH3可能参与了这一活性，并参与了对JNKs-c-Jun激活的抑制。(C)2007 Elsevier B.V.保留所有权利。
Wogonin (Wog; 5,7-dihydroxy-8-methoxy flavone) has been shown to effectively inhibit lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) gene expression and nitric oxide production in our previous study. In the present study, we found that Nor-wogonin (N-Wog; 5,7,8-trihydroxyl flavone), a structural analogue of Wog with an OH substitution at C8, performed different effect on LPS- or lipoteichoic acid (LTA)-induced iNOS gene expression and nitric oxide (NO) production in macrophages. Wog, but not N-Wog, significantly inhibits LPS- or LTA-induced NO production through suppressing iNOS gene expression at both protein and mRNA without affecting NO donor sodium nitroprusside-induced NO production, NOS enzyme activity, and cells viability. Activation of JNKs (not ERKs) via phosphorylation induction, and an increase in c-Jun (not c-Fos) protein expression were involved in LPS- and LTA-treated RAW264.7 cells, and those events were blocked by Wog, but not N-Wog, addition. Furthermore, 5,7-diOH flavone, but not 5-OH flavone, 7-OH flavone, 5-OH-7-OCH3 flavone, significantly inhibits LPS-induced iNOS protein expression and NO production, and 7,8-diOCH(3) flavone performs more effective inhibitory activity on LPS-induced NO production and iNOS protein expression than 7-OCH3-8-OH flavone. These data suggest that OHs at both C5 and C7 are essential for NO inhibition of flavonoids, and OCH3 at C8 may contribute to this activity, and suppression of JNKs-c-Jun activation is involved. (C) 2007 Elsevier B.V. All rights reserved.