Kwon Oh Eok, Lee Hyun Sun, Lee Seung Woong, Bae Kihwan, Kim Koanhoi, Hayashi Masahiko, Rho Mun-Chual, Kim Young-Kook
Laboratory of Lipid Metabolism, Korea Research Institute of Bioscience and Biotechnology, 52 Eoun-dong, Yusong-gu, Taejeon 305-333, Republic of Korea.
J Ethnopharmacol. 2006 Mar 8;104(1-2):270-7. doi: 10.1016/j.jep.2005.09.018. Epub 2005 Oct 17.
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.
在从天然来源寻找细胞粘附抑制剂的过程中，从日本金粟兰（金粟兰科）根部分离出三种活性化合物。这些化合物被鉴定为二聚倍半萜类化合物，分别为静香二醇B（1）、环静香二醇A（2）和静香二醇F（3）。这些化合物抑制佛波醇肉豆蔻酸酯乙酸酯（PMA）诱导的HL-60细胞同型聚集，且无细胞毒性，其最小抑菌浓度（MIC）值分别为34.1 nM（1）、0.9 μM（2）和27.3 nM（3）。虽然化合物1 - 3不影响淋巴细胞功能相关抗原-1（LFA-1）与细胞间粘附分子-1（ICAM-1）的直接结合，但这些化合物以剂量依赖性方式显著抑制HL-60细胞中ICAM-1的表达。另一方面，当人脐静脉内皮细胞（HUVEC）用化合物1 - 3预处理并用肿瘤坏死因子-α（TNF-α）刺激时，THP-1细胞与HUVEC的粘附呈剂量依赖性降低，其半数抑制浓度（IC50）值分别为54.6 nM、1.2 μM和34.1 nM。事实上，化合物1抑制TNF-α诱导的HUVEC中ICAM-1、血管细胞粘附分子-1（VCAM-1）和E-选择素的表面表达，其IC50值分别为5.4 nM、13.6 μM和95.6 nM。目前的研究结果表明，化合物1 - 3通过抑制TNF-α刺激的细胞粘附分子表达来阻止单核细胞与HUVEC的粘附。
