Biochemical Pharmacology Volume 73, Issue 10 , 15 May 2007, Pages 1602-1612
doi:10.1016/j.bcp.2007.01.015 Copyright © 2007 Elsevier Inc. All rights reserved.
Isoliquiritigenin inhibits IκB kinase activity and ROS generation to block TNF-α induced expression of cell adhesion molecules on human endothelial cells
Sarvesh Kumara, Amit Sharmaa, Babita Madana, Vandana Singhala and Balaram Ghosh, a,
aMolecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, University of Delhi Campus (North), Mall Road, Delhi 110007, India
Received 4 October 2006; accepted 9 January 2007. Available online 13 January 2007.
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.
Keywords: Cell adhesion molecules; Endothelial cells; IκBα; Isoliquiritigenin; NF-κB; ROS
Abbreviations: CAMs, cell adhesion molecules; ICAM-1, intercellular adhesion molecule-1; VCAM-1, vascular cell adhesion molecule-1; TNF-α, tumor necrosis factor-α; NF-κB, nuclear factor-κB; EMSA, electrophoretic mobility shift assay; HUVECs, human umbilical cord vein endothelial cells; NEMO, NF-κB essential modulator |