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

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-alpha induced adhesion of neutrophils to endothelial monolayer by blocking the expression of ICAM-1, VCAM-1 and E-selectin. Since NF-kappaB is a major transcription factor involved in the transcriptional regulation of cell adhesion molecules, thus we studied the status of NF-kappaB activation in ILTG treated endothelial cells. We demonstrate that ILTG inhibits the translocation and activation of nuclear factor-kappaB (NF-kappaB) by blocking the phosphorylation and subsequent degradation of IkappaBalpha. As oxidative stress is also known to regulate the activation of NF-kappaB 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.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Kumar S,Sharma A,Madan B,Singhal V,Ghosh B

doi

10.1016/j.bcp.2007.01.015

subject

Has Abstract

pub_date

2007-05-15 00:00:00

pages

1602-12

issue

10

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(07)00027-5

journal_volume

73

pub_type

杂志文章

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