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

被引:411
作者
Garcia-Mediavilla, Victoria
Crespo, Irene
Collado, Pilar S.
Esteller, Alejandro
Sanchez-Campos, Sonia
Tunon, Maria J.
Gonzalez-Gallego, Javier [1 ]
机构
[1] Univ Leon, Inst Biomed, E-24071 Leon, Spain
[2] Univ Salamanca, Dept Physiol & Pharmacol, Salamanca 37071, Spain
关键词
quercetin; kaempferol; nuclear factor kappa B; nitric oxide; C-reactive protein; inflammation; liver;
D O I
10.1016/j.ejphar.2006.11.014
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:221 / 229
页数:9
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