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Blockade of nuclear factor-kappaB signaling pathway and anti-inflammatory activity of cardamomin, a chalcone analog from Alpinia conchigera.
J Pharmacol Exp Ther. 2006 Jan; 316(1):271-8.JP

Abstract

Nuclear factor-kappaB (NF-kappaB) and the signaling pathways that regulate its activity have become a focal point for intense drug discovery and development efforts. NF-kappaB regulates the transcription of a large number of genes, particularly those involved in immune, inflammatory, and antiapoptotic responses. In our search for NF-kappaB inhibitors from natural resources, we identified cardamomin, 2',4'-dihydroxy-6'-methoxychalcone, as an inhibitor of NF-kappaB activation from Alpinia conchigera Griff (Zingiberaceae). In present study, we demonstrated the effect of cardamomin on NF-kappaB activation in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and LPS-induced mortality. This compound significantly inhibited the induced expression of NF-kappaB reporter gene by LPS or tumor necrosis factor (TNF)-alpha in a dose-dependent manner. LPS-induced production of TNF-alpha 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 kappaBalpha (IkappaBalpha) but also activation of inhibitor kappaB (IkappaB) kinases and nuclear translocation of NF-kappaB. Further analyses revealed that cardamomin did not directly inhibit IkappaB 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-kappaB. 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-alpha. Together, cardamomin could be valuable candidate for the intervention of NF-kappaB-dependent pathological condition such as inflammation.

Authors+Show Affiliations

Anticancer Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yuseong, Daejeon 305-600, Korea. jjlee@kribb.re.krNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16183703

Citation

Lee, Jeong-Hyung, et al. "Blockade of Nuclear factor-kappaB Signaling Pathway and Anti-inflammatory Activity of Cardamomin, a Chalcone Analog From Alpinia Conchigera." The Journal of Pharmacology and Experimental Therapeutics, vol. 316, no. 1, 2006, pp. 271-8.
Lee JH, Jung HS, Giang PM, et al. Blockade of nuclear factor-kappaB signaling pathway and anti-inflammatory activity of cardamomin, a chalcone analog from Alpinia conchigera. J Pharmacol Exp Ther. 2006;316(1):271-8.
Lee, J. H., Jung, H. S., Giang, P. M., Jin, X., Lee, S., Son, P. T., Lee, D., Hong, Y. S., Lee, K., & Lee, J. J. (2006). Blockade of nuclear factor-kappaB signaling pathway and anti-inflammatory activity of cardamomin, a chalcone analog from Alpinia conchigera. The Journal of Pharmacology and Experimental Therapeutics, 316(1), 271-8.
Lee JH, et al. Blockade of Nuclear factor-kappaB Signaling Pathway and Anti-inflammatory Activity of Cardamomin, a Chalcone Analog From Alpinia Conchigera. J Pharmacol Exp Ther. 2006;316(1):271-8. PubMed PMID: 16183703.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blockade of nuclear factor-kappaB signaling pathway and anti-inflammatory activity of cardamomin, a chalcone analog from Alpinia conchigera. AU - Lee,Jeong-Hyung, AU - Jung,Haeng Sun, AU - Giang,Phan Minh, AU - Jin,Xuejun, AU - Lee,Sangku, AU - Son,Phan Tong, AU - Lee,Dongho, AU - Hong,Young-Soo, AU - Lee,Kyeong, AU - Lee,Jung Joon, Y1 - 2005/09/23/ PY - 2005/9/27/pubmed PY - 2006/4/1/medline PY - 2005/9/27/entrez SP - 271 EP - 8 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 316 IS - 1 N2 - Nuclear factor-kappaB (NF-kappaB) and the signaling pathways that regulate its activity have become a focal point for intense drug discovery and development efforts. NF-kappaB regulates the transcription of a large number of genes, particularly those involved in immune, inflammatory, and antiapoptotic responses. In our search for NF-kappaB inhibitors from natural resources, we identified cardamomin, 2',4'-dihydroxy-6'-methoxychalcone, as an inhibitor of NF-kappaB activation from Alpinia conchigera Griff (Zingiberaceae). In present study, we demonstrated the effect of cardamomin on NF-kappaB activation in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and LPS-induced mortality. This compound significantly inhibited the induced expression of NF-kappaB reporter gene by LPS or tumor necrosis factor (TNF)-alpha in a dose-dependent manner. LPS-induced production of TNF-alpha 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 kappaBalpha (IkappaBalpha) but also activation of inhibitor kappaB (IkappaB) kinases and nuclear translocation of NF-kappaB. Further analyses revealed that cardamomin did not directly inhibit IkappaB 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-kappaB. 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-alpha. Together, cardamomin could be valuable candidate for the intervention of NF-kappaB-dependent pathological condition such as inflammation. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/16183703/Blockade_of_nuclear_factor_kappaB_signaling_pathway_and_anti_inflammatory_activity_of_cardamomin_a_chalcone_analog_from_Alpinia_conchigera_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16183703 DB - PRIME DP - Unbound Medicine ER -