Inhibition of tumor necrosis factor-α-induced expression of adhesion molecules in human endothelial cells by the saponins derived from roots of Platyeodon grandiflorum

Adhesion molecules play an important role in the development of atherogenesis and are produced by endothelial cells after being stimulated with various inflammatory cytokines. This study examined the effect of saponins that were isolated from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil saponins (CKS), on the cytokine-induced monocyte/human endothelial cell interaction, which is a crucial early event in atherogenesis. CKS significantly inhibited the TNF alpha-induced increase in monocyte adhesion to endothelial cells as well as decreased the protein and mRNA expression levels of vascular adhesion molecule-1 and intercellular cell adhesion molecule-1 on endothelial cells. Furthermore, CKS significantly inhibited the TNF alpha-induced production of intracellular reactive oxygen species (ROS) and activation of NF-kappa B by preventing I kappa B degradation and inhibiting I kappa B kinase activity. Overall, CKS has anti-atherosclerotic and anti-inflammatory activity, which is least in part the result of it reducing the cytokine-induced endothelial adhesion to monocytes by inhibiting intracellular ROS production, NF-kappa B activation, and cell adhesion molecule expression in endothelial cells. (c) 2005 Elsevier Inc. All rights reserved.