Andrographolide Inhibits ICAM-1 Expression and NF-κB Activation in TNF-α-Treated EA.hy926 Cells

• Published in: Journal of agricultural and food chemistry Vol. 59; no. 10; pp. 5263 - 5271
• Main Authors: Chao, Che-Yi, Lii, Chong-Kuei, Tsai, I-Ting, Li, Chien−Chun, Liu, Kai-Li, Tsai, Chia-Wen, Chen, Haw-Wen
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 25.05.2011
• Subjects: adhesion; Andrographis paniculata; anti-inflammatory activity; Anti-Inflammatory Agents - pharmacology; atherosclerosis; Bioactive Constituents; Biological and medical sciences; Cardiovascular Diseases - prevention & control; cell adhesion; Cell Adhesion - drug effects; Cell Line; Diterpenes - pharmacology; DNA; endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - physiology; Food industries; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; HL-60 Cells; Humans; inflammation; Intercellular Adhesion Molecule-1 - analysis; Intercellular Adhesion Molecule-1 - genetics; messenger RNA; NF-kappa B - antagonists & inhibitors; phosphorylation; protein synthesis; RNA, Messenger - analysis; signal transduction; small interfering RNA; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - pharmacology; NF-κB; ICAM-1; TNF-α; EA.hy926 cells; andrographolide; B; NF; Activation; Cell
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf104003y

Several lines of evidence indicate that inflammation and endothelial cell dysfunction are important initiating events in atherosclerosis. Tumor necrosis factor-α (TNF-α), 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 in Andrographis paniculata that has anti-inflammatory activity. A previous study demonstrated the role of heme oxygenase 1 (HO-1) in the inhibition of TNF-α-induced ICAM-1 expression by AP. The present study investigated the effect of AP on the IKK/NF-κB signaling pathway, which mediates TNF-α-induced ICAM-1 expression in EA.hy926 cells. Similar to the previous study, AP inhibited TNF-α-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-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. 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-α-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.