Blockade of nuclear factor-κB signaling pathway and anti-inflammatory activity of cardamomin, a chalcone analog from Alpinia conchigera

Jeong Hyung Lee, Sun Jung Haeng, Minh Giang Phan, Xuejun Jin, Sangku Lee, Tong Son Phan, Dongho Lee, Young S. Hong, Kyeong Lee, Joon Lee Jung

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

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 NH 2-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.

Original languageEnglish
Pages (from-to)271-278
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume316
Issue number1
DOIs
Publication statusPublished - 2006 Jan 1
Externally publishedYes

Fingerprint

Alpinia
Chalcone
Lipopolysaccharides
Anti-Inflammatory Agents
Phosphotransferases
Tumor Necrosis Factor-alpha
Phosphorylation
Zingiberaceae
Mortality
cardamonin
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases
Nitric Oxide Synthase Type II
Drug Discovery
Cyclooxygenase 2
Heat-Shock Proteins
Inbred C57BL Mouse
Reporter Genes
Protein Kinases
Inflammation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Blockade of nuclear factor-κB signaling pathway and anti-inflammatory activity of cardamomin, a chalcone analog from Alpinia conchigera. / Lee, Jeong Hyung; Haeng, Sun Jung; Phan, Minh Giang; Jin, Xuejun; Lee, Sangku; Phan, Tong Son; Lee, Dongho; Hong, Young S.; Lee, Kyeong; Jung, Joon Lee.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 316, No. 1, 01.01.2006, p. 271-278.

Research output: Contribution to journalArticle

Lee, Jeong Hyung ; Haeng, Sun Jung ; Phan, Minh Giang ; Jin, Xuejun ; Lee, Sangku ; Phan, Tong Son ; Lee, Dongho ; Hong, Young S. ; Lee, Kyeong ; Jung, Joon Lee. / Blockade of nuclear factor-κB signaling pathway and anti-inflammatory activity of cardamomin, a chalcone analog from Alpinia conchigera. In: Journal of Pharmacology and Experimental Therapeutics. 2006 ; Vol. 316, No. 1. pp. 271-278.
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AU - Jin, Xuejun

AU - Lee, Sangku

AU - Phan, Tong Son

AU - Lee, Dongho

AU - Hong, Young S.

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AU - Jung, Joon Lee

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