Dimeric sesquiterpenoids isolated from Chloranthus japonicus inhibited the expression of cell adhesion molecules.
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.
Kwon
Oh Eok
OE
Laboratory of Lipid Metabolism, Korea Research Institute of Bioscience and Biotechnology, 52 Eoun-dong, Yusong-gu, Taejeon 305-333, Republic of Korea.
Lee
Hyun Sun
HS
Lee
Seung Woong
SW
Bae
Kihwan
K
Kim
Koanhoi
K
Hayashi
Masahiko
M
Rho
Mun-Chual
MC
Kim
Young-Kook
YK
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*
D015815:Cell Adhesion Molecules; D010936:Plant Extracts; D012717:Sesquiterpenes