Manassantin A and B isolated from Saururus chinensis inhibit TNF-alpha-induced cell adhesion molecule expression of human umbilical vein endothelial cells.
Leukocyte adhesion to the vascular endothelium is a critical initiating step in inflammation and atherosclerosis. We have herein studied the effect of manassantin A (1) and B (2), dineolignans, on interaction of THP-1 monocytic cells and human umbilical vein endothelial cells (HUVEC) and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in HUVEC. When HUVEC were pretreated with 1 and 2 followed by stimulation with TNF-alpha, adhesion of THP-1 cells to HUVEC decreased in dose-dependent manner with IC50 values of 5 ng/mL and 7 ng/mL, respectively, without cytotoxicity. Also, 1 and 2 inhibited TNF-alpha-induced up-regulation of ICAM-1, VCAM-1 and E-selectin. The present findings suggest that 1 and 2 prevent monocyte adhesion to HUVEC through the inhibition of ICAM-1, VCAM-1 and E-selectin expression stimulated by TNF-alpha, and may imply their usefulness for the prevention of atherosclerosis relevant to endothelial activation.
Kwon
Oh Eok
OE
Laboratory of Lipid Metabolism, Korea Research Institute of Bioscience and Biotechnology, Taejeon, Korea.
Lee
Hyun Sun
HS
Lee
Seung Woong
SW
Chung
Mi Yeon
MY
Bae
Ki Hwan
KH
Rho
Mun-Chual
MC
Kim
Young-Kook
YK
D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D017705:Lignans; D032134:Saururaceae; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
D015815:Cell Adhesion Molecules; D005663:Furans; D017705:Lignans; D014409:Tumor Necrosis Factor-alpha; C482885:manassantin B; C054895:manassantin A