Cardamonin inhibits COX and iNOS expression via inhibition of p65NF-kappaB nuclear translocation and Ikappa-B phosphorylation in RAW 264.7 macrophage cells.
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.
Israf
D A
DA
Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. daud@medic.upm.edu.my
Khaizurin
T A
TA
Syahida
A
A
Lajis
N H
NH
Khozirah
S
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation; D020672:I-kappa B Proteins / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010766:Phosphorylation; D051996:Transcription Factor RelA / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D047188:Chalcones; D052246:Cyclooxygenase 2 Inhibitors; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; C000606205:Nfkbia protein, mouse; D009573:Nitrites; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C436747:cardamonin; D015232:Dinoprostone