Dehydrodiisoeugenol, an isoeugenol dimer, inhibits lipopolysaccharide-stimulated nuclear factor kappa B activation and cyclooxygenase-2 expression in macrophages
Dehydrodiisoeugenol, an isoeugenol dimer, inhibits lipopolysaccharide-stimulated nuclear factor kappa B activation and cyclooxygenase-2 expression in macrophages
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DOI：
10.1016/j.abb.2004.11.013
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发表时间：
2005-02-15
影响因子：
3.9
通讯作者：
Fujisawa, S
中科院分区：
文献类型：
--
作者：
Murakami, Y;Shoji, M;Fujisawa, S
邻甲氧基酚如丁香酚和异丁香酚表现出抗氧化和抗炎活性，但在较高浓度下充当氧化剂和有效的过敏原。我们最近证明丁香酚二聚体双丁香酚是一种有效的抑制脂多糖（LPS）诱导的巨噬细胞中的炎性细胞因子的表达，而没有细胞毒性。这一结果表明，邻甲氧基酚二聚体化合物可能具有抗炎活性。因此，我们进一步从异丁香酚合成了脱氢二异丁香酚和α-二异丁香酚，并研究了这些二聚体是否能抑制LPS刺激的核因子κ B（NF-κ B）活化和环氧化酶（考克斯）-2基因表达，这两种基因都与炎症和突变密切相关。脱氢二异丁子香酚可明显抑制LPS刺激的RAW 264.7小鼠巨噬细胞考克斯-2基因的表达。脱氢二异丁子香酚还显著抑制LPS刺激的抑制因子kappaB-α的磷酸化依赖性蛋白水解和NF-κ B的转录活性。这些发现表明，脱氢二异丁香酚作为一种有效的抗炎剂。(C)2004年爱思唯尔公司All rights reserved.
o-Methoxyphenols such as eugenol and isoeugenol exhibit anti-oxidant and anti-inflammatory activities, but at higher concentrations act as oxidants and potent allergens. We recently demonstrated the eugenol dimer bis-eugenol to be an efficient inhibitor of lipopolysaccharide (LPS)-induced inflammatory cytokine expression in macrophages without cytotoxicity. This result suggested that dimer compound of o-methoxyphenols may possess anti-inflammatory activity. Thus, we further synthesized dehydrodiisoeugenol and alpha-diisoeugenol from isoeugenols, and investigated whether these dimers Could inhibit LPS-stimulated nuclear factor kappa B (NF-kappaB) activation and cyclooxygenase (COX)-2 gene expression, both of which are closely involved in inflammation and mutagenesis. The expression of the COX-2 gene was strongly inhibited by dehydrodiisoeugenol in RAW264.7 murine macrophages stimulated with LPS. In contrast, isoeugenol and alpha-diisoeugenol did not inhibit it. Dehydrodiisoeugenol also significantly inhibited LPS-stimulated phosphorylation-dependent proteolysis of inhibitor kappaB-alpha and transcriptional activity of NF-kappaB in the cells. These findings suggest that dehydrodiisoeugenol acts as a potent anti-inflammatory agent. (C) 2004 Elsevier Inc. All rights reserved.