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

Eur J Pharmacol. 2007 Feb 28;557(2-3):221-9. doi: 10.1016/j.ejphar.2006.11.014. Epub 2006 Nov 15.

Abstract

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-kappaB) 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 micromol/l). Kaempferol produced a significant concentration-dependent decrease of iNOS, 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-kappaB activation and on protein concentration of the phosphorylated form of the inhibitor IkappaB alpha and of IKK (IkappaB kinase)alpha. The present study suggests that the modulation of iNOS, 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-kappaB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • C-Reactive Protein / analysis
  • C-Reactive Protein / antagonists & inhibitors*
  • Cell Line
  • Cyclooxygenase 2 / analysis
  • Cyclooxygenase 2 / metabolism*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Flavonols / chemistry
  • Flavonols / pharmacology
  • Hepatocytes / drug effects*
  • Hepatocytes / enzymology
  • Humans
  • Kaempferols / chemistry
  • Kaempferols / pharmacology*
  • Molecular Structure
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase Type II / analysis
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Quercetin / chemistry
  • Quercetin / pharmacology*

Substances

  • Flavonols
  • Kaempferols
  • NF-kappa B
  • kaempferol
  • C-Reactive Protein
  • Quercetin
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2