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.
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.
García-Mediavilla
Victoria
V
Institute of Biomedicine, University of León, 24071 León, Spain.
Crespo
Irene
I
Collado
Pilar S
PS
Esteller
Alejandro
A
Sánchez-Campos
Sonia
S
Tuñón
María J
MJ
González-Gallego
Javier
J
D002097:C-Reactive Protein / Q000032:analysis / Q000037:antagonists & inhibitors*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D044948:Flavonols / Q000737:chemistry / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D044949:Kaempferols / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000037:antagonists & inhibitors*; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*
D044948:Flavonols; D044949:Kaempferols; D016328:NF-kappa B; C006552:kaempferol; D002097:C-Reactive Protein; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2