Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase and tumor necrosis factor-α by 2′-hydroxychalcone derivatives in RAW 264.7 cells
Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase and tumor necrosis factor-α by 2′-hydroxychalcone derivatives in RAW 264.7 cells
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DOI：
10.1016/j.bcp.2003.12.016
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发表时间：
2004-04-15
影响因子：
5.8
通讯作者：
Ohuchi, K
中科院分区：
文献类型：
--
作者：
Ban, HS;Suzuki, K;Ohuchi, K
在小鼠巨噬细胞系RAW 264.7的培养物中，观察了四种2 ′-羟基查耳酮衍生物、2 ′-羟基-4 ′-甲氧基查耳酮、2 ′-羟基-4 ′-甲氧基查耳酮和2 ′-羟基-4 ′-甲氧基查耳酮对小鼠巨噬细胞系RAW 264.7的作用。（化合物1），2 '，4-二羟基-4'-甲氧基查耳酮（化合物2），2，4-二羟基-6 '-甲氧基查耳酮（化合物3）和2-羟基-4，4 '-二甲氧基查耳酮（化合物4）对脂多糖（LPS）诱导的一氧化氮（NO）和肿瘤坏死因子（TNF）-α产生的影响。3-30 μ M的化合物1、2和3以几乎相同的效力抑制产生。化合物4没有显示出抑制活性。3-30 μ M的化合物1、2和3抑制LPS诱导的诱导型一氧化氮合酶（iNOS）和TNF-α mRNA的表达。为了阐明所涉及的机制，检测了化合物1、2和3对核因子（NF）-κ B和激活蛋白-1（AP-1）的激活的影响。LPS诱导的NF-κ B和AP-1的活化均被3-30 μ M的化合物1、2和3阻断。这些结果表明，2 '-羟基查耳酮衍生物抑制LPS诱导的NO和TNF-α的产生是由于抑制NF-κ B和AP-1的激活。(C)2004爱思唯尔公司All rights reserved.
In cultures of the murine macrophage cell line RAW 264.7, effects of four 2'-hydroxychalcone derivatives, 2'-hydroxy-4'-methoxychalcone (compound 1), 2',4-dihydroxy-4'-methoxychalcone (compound 2), 2,4-dihydroxy-6'-methoxychalcone (compound 3) and 2-hydroxy-4,4'-dimethoxychalcone (compound 4), on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha were examined. Compounds 1, 2 and 3 at 3-30 muM inhibited the production with almost the same potency. Compound 4 showed no inhibitory activity. Compounds 1, 2 and 3 at 3-30 muM inhibited the LPS-induced expression of inducible nitric oxide synthase (iNOS) and TNF-alpha mRNA. To clarify the mechanism involved, effects of compounds 1, 2 and 3 on the activation of nuclear factor (NF)-kappaB and activator protein-1 (AP-1) were examined. Both the LPS-induced activation of NF-kappaB and AP-1 were blocked by compounds 1, 2 and 3 at 3-30 muM. Moreover, the three compounds at such concentrations inhibited the LPS-induced IkappaB degradation and the phosphorylation of c-jun N-terminal kinase (JNK) and c-jun. These findings suggest that the inhibition of the LPS-induced production of NO and TNF-alpha by the 2'-hydroxychalcone derivatives is due to the inhibition of NF-kappaB and AP-1 activations. (C) 2004 Elsevier Inc. All rights reserved.