Dimeric sesquiterpenoids isolated from Chloranthus japonicus inhibited the expression of cell adhesion molecules
2006
Kwon, O.E. | Lee, H.S. | Lee, S.W. | Bae, K.H. | Kim, K. | Hayashi, M. | Rho, M.C. | Kim, Y.K.
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 μM (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-α, adhesion of THP-1 cells to HUVEC decreased in dose-dependent manner with IC50 values of 54.6 nM, 1.2 μM and 34.1 nM, respectively. In fact, 1 inhibited TNF-α-induced surface expression of the ICAM-1, VCAM-1 and E-selectin in HUVEC with IC50 values of 5.4 nM, 13.6 μM 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-α.
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