Effects of diarylheptanoids on the tumor necrosis factor-alpha-induced expression of adhesion molecules in human umbilical vein endothelial cells.
Atherosclerosis is a chronic inflammatory disease that is characterized by infiltration of mononuclear lymphocytes into the intima through the expression of adhesion molecules on the arterial wall. In the present study, we report the inhibitory effects of two diarylheptanoids, 5-O-methylhirsutanonol (1) and oregonin (2), isolated from the methanolic extracts of Alnus japonica leaves, on the expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). Compounds 1 and 2 inhibited tumor necrosis factor (TNF)-alpha-induced up-regulation of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), which also prevented adhesion of monocytes to HUVECs, and slightly suppressed the mRNA expression of the inflammation-associated gene interleukin-1beta (IL-1beta). A further study demonstrated the inhibitory effect of compound 1 on DNA-binding of nuclear factor kappaB (NF-kappaB) and on the phosphorylation and degradation of inhibitory factor kappaBalpha (IkappaBalpha) in TNF-alpha-stimulated HUVECs. These results indicate that compounds 1 and 2 may be useful in the prevention and treatment of atherosclerosis through attenuation of adhesion molecule expression by inhibition of NF-kappaB activation.
Han
Jong-Min
JM
National Research Laboratory of Lipid Metabolism & Atherosclerosis, Bio-Evaluation Center, KRIBB, Daejeon 305-806, Korea.
Lee
Woo Song
WS
Kim
Ju-Ryoung
JR
Son
Joonsok
J
Nam
Ki-Hoan
KH
Choi
Seung-Chul
SC
Lim
Jong-Seok
JS
Jeong
Tae-Sook
TS
D029661:Alnus / Q000737:chemistry; D036381:Diarylheptanoids / Q000494:pharmacology*; D042783:Endothelial Cells / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D010936:Plant Extracts / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
D036381:Diarylheptanoids; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C409456:oregonin; D018799:Intercellular Adhesion Molecule-1