PT  - JOURNAL ARTICLE
AU  - Jeong-Hyung Lee
AU  - Haeng Sun Jung
AU  - Phan Minh Giang
AU  - Xuejun Jin
AU  - Sangku Lee
AU  - Phan Tong Son
AU  - Dongho Lee
AU  - Young-Soo Hong
AU  - Kyeong Lee
AU  - Jung Joon Lee
TI  - Blockade of Nuclear Factor-κB Signaling Pathway and Anti-Inflammatory Activity of Cardamomin, a Chalcone Analog from <em>Alpinia conchigera</em>
AID  - 10.1124/jpet.105.092486
DP  - 2006 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 271--278
VI  - 316
IP  - 1
4099  - http://jpet.aspetjournals.org/content/316/1/271.short
4100  - http://jpet.aspetjournals.org/content/316/1/271.full
SO  - J Pharmacol Exp Ther2006 Jan 01; 316
AB  - Nuclear factor-κB (NF-κB) and the signaling pathways that regulate its activity have become a focal point for intense drug discovery and development efforts. NF-κB regulates the transcription of a large number of genes, particularly those involved in immune, inflammatory, and antiapoptotic responses. In our search for NF-κB inhibitors from natural resources, we identified cardamomin, 2′,4′-dihydroxy-6′-methoxychalcone, as an inhibitor of NF-κB activation from Alpinia conchigera Griff (Zingiberaceae). In present study, we demonstrated the effect of cardamomin on NF-κB activation in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and LPS-induced mortality. This compound significantly inhibited the induced expression of NF-κB reporter gene by LPS or tumor necrosis factor (TNF)-α in a dose-dependent manner. LPS-induced production of TNF-α and NO as well as expression of inducible nitric-oxide synthase and cyclooxygenase-2 was significantly suppressed by the treatment of cardamomin in RAW264.7 cells. Also, cardamomin inhibited not only LPS-induced degradation and phosphorylation of inhibitor κBα (IκBα) but also activation of inhibitor κB (IκB) kinases and nuclear translocation of NF-κB. Further analyses revealed that cardamomin did not directly inhibit IκB kinases, but it significantly suppressed LPS-induced activation of Akt. Moreover, cardamomin suppressed transcriptional activity and phosphorylation of Ser536 of RelA/p65 subunit of NF-κB. However, this compound did not inhibit LPS-induced activation of extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun NH2-terminal kinase, but significantly impaired activation of p38 mitogen-activated protein kinase. We also demonstrated that pretreatment of cardamomin rescued C57BL/6 mice from LPS-induced mortality in conjunction with decreased serum level of TNF-α. Together, cardamomin could be valuable candidate for the intervention of NF-κB-dependent pathological condition such as inflammation. The American Society for Pharmacology and Experimental Therapeutics