Antiplatelet, anticoagulant, and profibrinolytic activities of withaferin A
Antiplatelet, anticoagulant, and profibrinolytic activities of withaferin A
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DOI：
10.1016/j.vph.2014.01.009
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发表时间：
2014-03-01
影响因子：
4
通讯作者：
Bae, Jong-Sup
中科院分区：
文献类型：
--
作者：
Ku, Sae-Kwang;Bae, Jong-Sup
Withaferin A （WFA）是一种来自Withania somnifera的活性化合物，因其抗炎、心脏活性和中枢神经系统作用而被广泛研究。然而，WFA的抗血小板、抗凝血和纤原蛋白溶解性能尚未被研究。在这项研究中，通过监测活化的部分凝血酶时间（aPTT），凝血酶原时间（PT），纤维蛋白聚合，血小板聚集，血栓形成，以及基于细胞的凝血酶和活化因子X （FXa）的活性来测量WFA的抗凝活性。在肿瘤坏死因子- α (tnf - α)活化的人脐静脉内皮细胞（HUVECs）中检测了WFA对纤溶酶原激活物抑制剂1型（PAI-1）和组织型纤溶酶原激活物（t-PA）表达的影响。我们的数据显示，WFA抑制凝血酶催化的纤维蛋白聚合和血小板聚集。feci3诱导血栓形成，显著延长aPTT和PT，抑制凝血酶和FXa的活性和产生。WFA延长了体内和体外出血时间，抑制了tnf - α诱导的PAI-1的产生。此外，WFA显著降低了PAI-1/t-PA比率。总之，这些结果表明WFA具有抗血栓活性，并提示本研究可为开发新的抗凝剂提供基础。(C) 2614 Elsevier Inc.版权所有。
Withaferin A (WFA), an active compound from Withania somnifera, is widely researched for its anti-inflammatory, cardioactive and central nervous system effects. However, antiplatelet, anticoagulant, and profibrinolytic properties of WFA have not been studied. In this study, the anticoagulant activities of WFA were measured by monitoring activated partial thromboplastin-time (aPTT), prothrombin time (PT), fibrin polymerization, platelet aggregation, thrombus formation, and the activities of cell-based thrombin and activated factor X (FXa). The effects of WFA on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-alpha (TNF-alpha) activated human umbilical vein endothelial cells (HUVECs). Our data showed that WFA inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. FeCI3-induced thrombus formation, prolonged aPTT and PT significantly and inhibited the activities and production of thrombin and FXa. WFA prolonged in vivo and ex vivo bleeding time and inhibited TNF-alpha induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by WFA. Collectively, these results indicate that WFA possesses antithrombotic activities and suggest that the current study could provide bases for the development of new anticoagulant agents. (C) 2614 Elsevier Inc. All rights reserved.