Triptolide inhibits murine-inducible nitric oxide synthase expression by down-regulating lipopolysaccharide-induced activity of nuclear factor-κB and c-Jun NH2-terminal kinase
Triptolide inhibits murine-inducible nitric oxide synthase expression by down-regulating lipopolysaccharide-induced activity of nuclear factor-κB and c-Jun NH2-terminal kinase
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DOI：
10.1016/j.ejphar.2004.04.040
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发表时间：
2004-06-21
影响因子：
5
通讯作者：
Kwon, TK
中科院分区：
文献类型：
--
作者：
Kim, YH;Lee, SH;Kwon, TK
雷公藤内酯醇（PG 490）是从中药雷公藤中提取的一种天然生物活性化合物。它已被证明具有有效的抗炎和免疫抑制特性。在Raw 264.7细胞刺激脂多糖（LPS）模拟炎症，雷公藤内酯醇抑制一氧化氮（NO）的产生，在剂量依赖性的方式和废除诱导型一氧化氮合酶（iNOS）基因的表达。为了研究雷公藤内酯醇抑制常规iNOS基因表达的机制，我们检测了这些细胞中丝裂原活化蛋白激酶（MAP激酶）和核因子-κ B（NF-κ B）的活化。雷公藤内酯醇抑制c-Jun氨基末端激酶（JNK）的磷酸化，但不抑制细胞外信号调节激酶（ERK）或p38丝裂原活化蛋白激酶的磷酸化。雷公藤内酯醇还能显著抑制NF-κ B的DNA结合活性。总之，这些结果表明，雷公藤内酯醇通过抑制NO的产生和iNOS的表达，通过阻断NF-κ B和JNK的激活来抑制炎症。(C)2004 Elsevier B. V.保留所有权利。
Triptolide (PG490) is a natural, biologically active compound extracted from the Chinese herb Tripterygium wilfordii. It has been shown to possess potent anti-inflammatory and imunnosuppressive properties. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, triptolide inhibits nitric oxide (NO) production in a dose-dependent manner and abrogates inducible nitric oxide synthase (iNOS) gene expression. To investigate the mechanism by which triptolide inhibits routine iNOS gene expression, we examined activation of mitogen-activated protein kinases (MAP kinases) and nuclear factor-kappaB (NF-kappaB) in these cells. Addition of triptolide inhibited phosphorylation of c-Jun NH2-terminal kinase (JNK) but not that of extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein kinase. In addition, triptolide significantly inhibited the DNA binding activity of NF-kappaB. Taken together, these results suggest that triptolide acts to inhibit inflammation through inhibition of NO production and iNOS expression through blockade of NF-kappaB and JNK activation. (C) 2004 Elsevier B.V. All rights reserved.