Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, 1370 Sankyuk-dong, Buk-gu, Daegu 702-701, Republic of Korea.
Food Chem Toxicol. 2011 Jul;49(7):1572-7. doi: 10.1016/j.fct.2011.04.003. Epub 2011 Apr 8.
Phloroglucinol is the monomeric units of phlorotannins abundant in brown algae. Several biological effects of phloroglucinol have been reported, however, antithrombotic and profibrinolytic activities of phloroglucinol have not been studied yet. In this study, the anticoagulant properties of phloroglucinol were determined by assays of activated partial thromboplastin time (aPTT), prothrombin time (PT) and cell based thrombin and activated factor X (FXa) generation activities. And the effects of phloroglucinol on the expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor-α (TNF-α) activated human endothelial cells (HUVECs). I found that phloroglucinol prolonged aPTT and PT significantly and inhibited thrombin and FXa generation in HUVECs. Furthermore, phloroglucinol inhibited TNF-α induced PAI-1 production. I then used pathway inhibitors to investigate which step of the TNF-α induced signaling pathway was targeted by phloroglucinol. I observed that the c-Jun N-terminal kinase (JNK) inhibitor increased the inhibitory effects of phloroglucinol, whereas the nuclear factor factor-κB (NF-κB) and the extracellular signal-regulated kinase (ERK) inhibitor did not. Therefore these results suggest that phloroglucinol possess antithrombotic and profibrinolytic activities and that NF-κB and ERK pathways are possible targets of phloroglucinol in the regulation of TNF-α stimulated PAI-1 production in HUVECs.
间苯三酚是富含于褐藻中的菲类单宁的单体单元。已有报道称间苯三酚具有多种生物学效应，然而，其抗血栓和纤维蛋白溶解活性尚未得到研究。在这项研究中，通过测定活化部分凝血活酶时间（aPTT）、凝血酶原时间（PT）以及基于细胞的凝血酶和活化因子 X（FXa）生成活性来确定间苯三酚的抗凝特性。并在肿瘤坏死因子-α（TNF-α）激活的人血管内皮细胞（HUVEC）中测试间苯三酚对纤溶酶原激活物抑制剂 1（PAI-1）和组织型纤溶酶原激活物（t-PA）表达的影响。结果发现，间苯三酚显著延长 aPTT 和 PT，并抑制 HUVEC 中凝血酶和 FXa 的生成。此外，间苯三酚抑制 TNF-α诱导的 PAI-1 产生。然后，我使用通路抑制剂来研究间苯三酚针对 TNF-α 诱导的信号通路的哪个步骤。我观察到 c-Jun N-末端激酶（JNK）抑制剂增加了间苯三酚的抑制作用，而核因子κB（NF-κB）和细胞外信号调节激酶（ERK）抑制剂则没有。因此，这些结果表明间苯三酚具有抗血栓和纤维蛋白溶解活性，并且 NF-κB 和 ERK 通路可能是间苯三酚在调节 TNF-α 刺激的 HUVECs 中 PAI-1 产生中的作用靶点。
