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. 2007 Feb;44(5):673-9.
doi: 10.1016/j.molimm.2006.04.025. Epub 2006 Jun 13.

Cardamonin Inhibits COX and iNOS Expression via Inhibition of p65NF-kappaB Nuclear Translocation and Ikappa-B Phosphorylation in RAW 264.7 Macrophage Cells

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Cardamonin Inhibits COX and iNOS Expression via Inhibition of p65NF-kappaB Nuclear Translocation and Ikappa-B Phosphorylation in RAW 264.7 Macrophage Cells

D A Israf et al. Mol Immunol. .

Abstract

Cardamonin, a chalcone isolated from the fruits of a local plant Alpinia rafflesiana, has demonstrated anti-inflammatory activity in cellular models of inflammation. In this report, we evaluated the ability of cardamonin to suppress both NO and PGE2 synthesis, iNOS and COX-2 expression and enzymatic activity, and key molecules in the NF-kappaB pathway in order to determine its molecular target. Cardamonin suppressed the production of NO and PGE2 in interferon-gamma (IFN-gamma)- and lipopolysaccharide (LPS)-induced RAW 264.7 cells. This inhibition was demonstrated to be caused by a dose-dependent down-regulation of both inducible enzymes, iNOS and COX-2, without direct effect upon iNOS or COX-2 enzyme activity. Subsequently we determined that the inhibition of inducible enzyme expression was due to a dose-dependent inhibition of phosphorylation and degradation of I-kappaBalpha, which resulted in a reduction of p65NF-kappaB nuclear translocation. We conclude that cardamonin is a potential anti-inflammatory drug lead that targets the NF-kappaB pathway.

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