Isoliquiritigenin inhibits IκB kinase activity and ROS generation to block TNF-α induced expression of cell adhesion molecules on human endothelial cells

Kumar, Sarvesh ; Sharma, Amit ; Madan, Babita ; Singhal, Vandana ; Ghosh, Balaram (2007) Isoliquiritigenin inhibits IκB kinase activity and ROS generation to block TNF-α induced expression of cell adhesion molecules on human endothelial cells Biochemical Pharmacology, 73 (10). pp. 1602-1612. ISSN 0006-2952

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Official URL: http://www.sciencedirect.com/science/article/pii/s...

Related URL: http://dx.doi.org/10.1016/j.bcp.2007.01.015

Abstract

Isoliquiritigenin (ILTG) is a flavonoid with chalcone structure (4,2',4'-trihydroxychalcone), an active component present in plants like Glycyrrhiza and Dalbergia which showed various biological activities including anti-inflammatory, anti-carcinogenic and antihistamic. As very little is known in regard to the underlying mechanism involved in explaining the various activities of the compound, we carried out a detailed study on the effect of ILTG on the expression of cell adhesion molecules on human primary endothelial cells. We demonstrate here that ILTG inhibits TNF-α induced adhesion of neutrophils to endothelial monolayer by blocking the expression of ICAM-1, VCAM-1 and E-selectin. Since NF-κB is a major transcription factor involved in the transcriptional regulation of cell adhesion molecules, thus we studied the status of NF-κB activation in ILTG treated endothelial cells. We demonstrate that ILTG inhibits the translocation and activation of nuclear factor-κB (NF-κB) by blocking the phosphorylation and subsequent degradation of IκBα. As oxidative stress is also known to regulate the activation of NF-κB to modulate TNF-α signaling cascade, we tested the effect of ILTG on reactive oxygen species (ROS). We found that it inhibits TNF-α induced ROS production in endothelial cells. These results have important implications for using ILTG or its derivatives towards the development of effective anti-inflammatory molecules.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Cell Adhesion Molecules; Endothelial Cells; IκBα; Isoliquiritigenin; NF-κB; ROS
ID Code:66038
Deposited On:21 Oct 2011 03:32
Last Modified:21 Oct 2011 03:32

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