The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells
The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells
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DOI：
10.1016/j.ejphar.2006.11.014
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发表时间：
2007-02-28
影响因子：
5
通讯作者：
Gonzalez-Gallego, Javier
中科院分区：
文献类型：
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作者：
Garcia-Mediavilla, Victoria;Crespo, Irene;Gonzalez-Gallego, Javier
我们研究了黄酮类化合物槲皮素和山奈酚调节诱导型一氧化氮合酶（iNOS），环氧合酶-2（考克斯-2）和反应性C蛋白（CRP）表达的能力，并诱导核因子κ B（NF-κ B）途径在人肝细胞衍生细胞系Chang Liver中的变化。将细胞与补充有槲皮素或山奈酚（5至200 μ mol/l）的细胞因子混合物一起孵育。山奈酚对NOS、考克斯-2和CRP蛋白表达的抑制作用呈浓度依赖性，但槲皮素对NOS、COX-2和CRP蛋白表达的抑制作用在高浓度时降低。两种黄酮类化合物均显著抑制iNOS、考克斯-2和CRP的mRNA水平。还观察到槲皮素和山奈酚对NF-κ B活化和抑制剂I κ B α和IKK（I κ B激酶）α磷酸化形式的蛋白浓度的抑制作用。本研究提示槲皮素或山奈酚对NOS、考克斯-2和CRP的调节可能通过阻断NF-κ B B的激活和促炎基因的上调而促进这两种结构相似的黄酮类化合物对Chang Liver细胞的抗炎作用。我们的数据还表明，这两种化合物之间的微小结构差异决定了它们的抑制能力的差异。(c)2006 Elsevier B. V.保留所有权利。
We examined the ability of the flavonoids quercetin and kaempferol to modulate inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and reactive C-protein (CRP) expression, and to induce changes in the nuclear factor kappa B (NF-kappa B) pathway in the human hepatocyte-derived cell line Chang Liver. Cells were incubated with a cytokine mixture supplemented with quercetin or kaempferol (5 to 200 mu mol/1). Kaempferol produced a significant concentration-dependent decrease of NOS, COX-2 and CRP protein level at all concentrations, but the percentage of inhibition induced by quercetin was reduced at high concentrations. Both flavonoids significantly inhibited mRNA level of iNOS, COX-2, and CRP. Inhibitory effects by quercetin and kaempferol were also observed on NF-kappa B activation and on protein concentration of the phosphorylated form of the inhibitor I kappa B alpha, and of IKK (I kappa B kinase)alpha. The present study suggests that the modulation of NOS, COX-2 and CRP by quercetin or kaempferol may contribute to the anti-inflammatory effects of these two structurally similar flavonoids in Chang Liver cells, via mechanisms likely to involve blockade of NF-kappa B activation and the resultant up-regulation of the pro-inflammatory genes. Our data also indicate that the minor structural differences between both compounds determine differences in their inhibitory capacity. (c) 2006 Elsevier B.V. All rights reserved.