"Several lines of evidence indicate that inflammation and endothelial cell dysfunction are important initiating events in
atherosclerosis. Tumor necrosis factor-R(TNF-R), a pro-inflammatory cytokine, induces the expression of cell adhesion molecules
and results in monocyte adherence and atheromatous plaque formation. Andrographolide (AP) is a major bioactive diterpene
lactone inAndrographis paniculata that has anti-inflammatory activity. A previous study demonstrated the role of heme oxygenase 1
(HO-1) in the inhibition of TNF-R-induced ICAM-1 expression by AP. The present study investigated the effect of AP on the IKK/
NF-κB signaling pathway, which mediates TNF-R-induced ICAM-1 expression in EA.hy926 cells. Similar to the previous study, AP
inhibited TNF-R-induced ICAM-1 mRNA and protein levels, its expression on the cell surface, and subsequent adhesion of HL-60
cells to EA.hy926 cells. AP inhibited TNF-R-induced κB inhibitor (IκB) kinase (IKK) and IκBR activation, p65 nuclear
translocation, NF-κB and DNA binding activity, and promoter activity of ICAM-1. Although AP increased the intracellular cAMP
concentration and induced the phosphorylation of cAMP response element-binding protein (CREB), knocking down CREB
protein expression by transfecting the cells with CREB-specific small interfering RNA did not relieve the inhibition of ICAM-1
expression by AP. Taken together, these results suggest that AP down-regulates TNF-R-induced ICAM-1 expression at least in part
via attenuation of activation of NF-κB in EA.hy926 cells rather than through activation of CREB. The results suggest that AP may
have potential as a cardiovascular-protective agent."
Relation:
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY; 59(10):5263-71.
