Inhibition of tumor necrosis factor-alpha-induced expression of adhesion molecules in human endothelial cells by the saponins derived from roots of Platycodon 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 TNFalpha-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 TNFalpha-induced production of intracellular reactive oxygen species (ROS) and activation of NF-kappaB by preventing IkappaB degradation and inhibiting IkappaB 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-kappaB activation, and cell adhesion molecule expression in endothelial cells.
Kim
Ji Young
JY
Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, Kwangju, South Korea.
Kim
Dong Hee
DH
Kim
Hyung Gyun
HG
Song
Gyu-Yong
GY
Chung
Young Chul
YC
Roh
Seong Hwan
SH
Jeong
Hye Gwang
HG
D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002460:Cell Line; D019040:E-Selectin / Q000096:biosynthesis; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry; D031238:Platycodon / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012503:Saponins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1