Quercetin attenuates nuclear factor-κB activation and nitric oxide production in interleukin-1β-activated rat hepatocytes

Abstract

We investigated whether different concentrations of the flavonoid quercetin ameliorate nitric oxide production and nuclear factor (NF)-κB activation in interleukin (IL)-1β-activated rat hepatocytes. Primary cultures of rat hepatocytes were treated with IL-1β alone or with quercetin in concentrations ranging from 5 to 100 μmol/L. The generation of reactive oxygen species, assessed by flow cytometry using dichlorodihydrofluorescein diacetate, was significantly reduced, and the oxidized:reduced glutathione ratio decreased in cultures treated with 50 and 100 μmol/L of quercetin. Quercetin at 100 μmol/L significantly prevented the IL-1β-induced release of nitrite into the culture medium. Western blot and reverse transcription-PCR analyses demonstrated that increased levels of inducible nitric oxide synthase (iNOS) protein and mRNA in hepatocytes stimulated by IL-1β were prevented by 50 μmol/L and 100 μmol/L of quercetin. Electrophoretic mobility shift assay experiments and Western blots indicated that quercetin blocked the activation of NF-κB and decreased the inhibitor êÂprotein levels induced by IL-1β. In summary, quercetin, a natural flavonol widely distributed in the human diet, inhibits NO production in IL-1β-stimulated hepatocytes through the inhibition of iNOS expression. Although the mode of action remains to be clarified, our findings support the view that the mechanism of action is via inhibition of IL-1β-induced NF-κB activation. © 2005 American Society for Nutritional Sciences.