Several lines of evidence indicate that inflammation and endothelial cell dysfunction are important initiating events in atherosclerosis. Tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, induces the expression of cell adhesion molecules and results in monocyte adherence and atheromatous plaques formation. Andrographolide (AP) is a major bioactive diterpene lactone in Andrographis paniculata, which possesses anti-inflammatory property. In the present study, we investigated the effect of AP on TNF-α-induced ICAM-1 expression in EA.hy926 cells. AP inhibited TNF-α-induced ICAM-1 mRNA, total protein, and cell-surface expressions. In addition, TNF-α-induced adhesion of HL-60 to EA.hy926 cells was abolished by AP. Furthermore, AP suppressed TNF-α-induced κB inhibitor (IκB) kinase (IKK) and IκBα activation, p65 nuclear translocation, NF-κB and DNA binding activity, and promoter activity of ICAM-1. AP increased intracellular cAMP concentration and induced the phosphorylation of cAMP response element-binding protein (CREB). Transfection with CREB-specific small interfering RNA knocked down CREB expression, however, did not inhibit ICAM-1 expression by AP. Taken together, these results suggest that AP down-regulates TNF-α-induced ICAM-1 expression via attenuation of activation of NF-κB in EA.hy926 cells. The results may implicate the cardiovascular-protective potential of AP.
