Journal
MOLECULAR IMMUNOLOGY
Volume 44, Issue 5, Pages 673-679Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2006.04.025
Keywords
cardamonin; NO; PGE(2); iNOS; COX-2; p65NF-kappa B; I-kappa B alpha
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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 PGE(2) synthesis, iNOS and COX-2 expression and enzymatic activity, and key molecules in the NF-kappa B 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-kappa B alpha, which resulted in a reduction of p65NF-kappa B nuclear translocation. We conclude that cardamonin is a potential anti-inflammatory drug lead that targets the NF-kappa B pathway. (c) 2006 Elsevier Ltd. All rights reserved.
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