title: Manassantin A and B isolated from Saururus chinensis inhibit TNF-alpha-induced cell adhesion molecule expression of human umbilical vein endothelial cells.
abstract: 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.
authors.affiliation: Laboratory of Lipid Metabolism, Korea Research Institute of Bioscience and Biotechnology, Taejeon, Korea.
authors.forename: Oh Eok
authors.initials: OE
authors.lastname: Kwon
authors.forename: Hyun Sun
authors.initials: HS
authors.lastname: Lee
authors.forename: Seung Woong
authors.initials: SW
authors.lastname: Lee
authors.forename: Mi Yeon
authors.initials: MY
authors.lastname: Chung
authors.forename: Ki Hwan
authors.initials: KH
authors.lastname: Bae
authors.forename: Mun-Chual
authors.initials: MC
authors.lastname: Rho
authors.forename: Young-Kook
authors.initials: YK
authors.lastname: Kim
mesh_terms: 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
chemical_list: D015815:Cell Adhesion Molecules; D005663:Furans; D017705:Lignans; D014409:Tumor Necrosis Factor-alpha; C482885:manassantin B; C054895:manassantin A