Cardamonin inhibits COX and iNOS expression via inhibition of p65NF-κB nuclear translocation and Iκ-B phosphorylation in RAW 264.7 macrophage cells
Israf Ali, Daud Ahmad and Tajul Arifin, Khaizurin and Ahmad, Syahida and Lajis, Md Nordin and Shari, Khozirah (2007) Cardamonin inhibits COX and iNOS expression via inhibition of p65NF-κB nuclear translocation and Iκ-B phosphorylation in RAW 264.7 macrophage cells. Molecular Immunology, 44 (5). pp. 673-679. ISSN 0161-5890
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Official URL: http://dx.doi.org/10.1016/j.molimm.2006.04.025
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-κB pathway in order to determine its molecular target. Cardamonin suppressed the production of NO and PGE2 in interferon-γ (IFN-γ)- 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-κBα, which resulted in a reduction of p65NF-κB nuclear translocation. We conclude that cardamonin is a potential anti-inflammatory drug lead that targets the NF-κB pathway.
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