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

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-alpha induced adhesion of neutrophils to endothelial monolayer by blocking the expression of ICAM-1, VCAM-1 and E-selectin. Since NF-kappa B is a major transcription factor involved in the transcriptional regulation of cell adhesion molecules, thus we studied the status of NF-kappa B activation in ILTG treated endothelial cells. We demonstrate that ILTG inhibits the translocation and activation of nuclear factor-kappa B (NF-kappa B) by blocking the phosphorylation and subsequent degradation of I kappa B alpha. As oxidative stress is also known to regulate the activation of NF-kappa B to modulate TNF-alpha signaling cascade, we tested the effect of ILTG on reactive oxygen species (ROS). We found that it inhibits TNF-alpha 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. (c) 2007 Elsevier Inc. All rights reserved.