title: Dimeric sesquiterpenoids isolated from Chloranthus japonicus inhibited the expression of cell adhesion molecules.
abstract: In the search for cell adhesion inhibitors from natural sources, three active compounds were isolated from Chloranthus japonicus Sieb. (Chloranthaceae) roots. The compounds were identified as dimeric sesquiterpenoids of shizukaol B (1), cycloshizukaol A (2) and shizukaol F (3). These compounds inhibited PMA-induced homotypic aggregation of HL-60 cells without cytotoxicity with MIC values of 34.1 nM (1), 0.9 microM (2) and 27.3 nM (3), respectively. Although 1-3 did not affect the direct binding of LFA-1 to ICAM-1, these compounds markedly inhibited ICAM-1 expression in HL-60 cells in a dose-dependent fashion. On the other hand, when HUVEC were pretreated with 1-3 and stimulated with TNF-alpha, adhesion of THP-1 cells to HUVEC decreased in dose-dependent manner with IC(50) values of 54.6 nM, 1.2 microM and 34.1 nM, respectively. In fact, 1 inhibited TNF-alpha-induced surface expression of the ICAM-1, VCAM-1 and E-selectin in HUVEC with IC(50) values of 5.4 nM, 13.6 microM and 95.6 nM, respectively. The present findings suggest that 1-3 prevent monocyte adhesion to HUVEC through the inhibition of cell adhesion molecules expression stimulated by TNF-alpha.
authors.affiliation: Laboratory of Lipid Metabolism, Korea Research Institute of Bioscience and Biotechnology, 52 Eoun-dong, Yusong-gu, Taejeon 305-333, Republic of 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: Kihwan
authors.initials: K
authors.lastname: Bae
authors.forename: Koanhoi
authors.initials: K
authors.lastname: Kim
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hayashi
authors.forename: Mun-Chual
authors.initials: MC
authors.lastname: Rho
authors.forename: Young-Kook
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000818:Animals; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018517:Plant Roots; D010946:Plants, Medicinal; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D015815:Cell Adhesion Molecules; D010936:Plant Extracts; D012717:Sesquiterpenes