Antithrombotic and antiplatelet activities of small-molecule alkaloids from Scolopendra subspinipes mutilans.
Antithrombotic and antiplatelet activities of small-molecule alkaloids from Scolopendra subspinipes mutilans.
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DOI：
10.1038/srep21956
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发表时间：
2016-02-24
影响因子：
4.6
通讯作者：
Bae JS
中科院分区：
文献类型：
--
作者：
Lee W;Lee J;Kulkarni R;Kim MA;Hwang JS;Na M;Bae JS
本研究旨在从少棘蜈蚣（Scolopendra subspinipes mutilans，SSM）中发现小分子抗凝剂。从少棘蜈蚣中分离出一种新的酰化多胺（1）和一种新的硫酸化喹啉生物碱（2）。用新生物碱1、2和吲哚乙酸4处理可延长活化部分凝血活酶时间和凝血酶原时间，并抑制凝血酶和活化因子X的活性及生成。此外，化合物1、2和4抑制凝血酶催化的纤维蛋白聚合和血小板聚集。与这些潜在的体外抗血小板活性相一致，化合物1、2和4在体内肺栓塞和动脉血栓形成模型中显示出增强的抗血栓作用。化合物1、2和4在小鼠中也引发抗凝作用。总体而言，本研究可为将少棘蜈蚣或化合物1、2和4作为功能性食品成分用于预防和治疗致病状况的商业化奠定基础，并为抗凝剂的开发提供新的支架。
The aim of this study was to discover small-molecule anticoagulants from Scolopendra subspinipes mutilans (SSM). A new acylated polyamine (1) and a new sulfated quinoline alkaloid (2) were isolated from SSM. Treatment with the new alkaloids 1, 2, and indole acetic acid 4 prolonged the activated partial thromboplastin time and prothrombin time and inhibited the activity and production of thrombin and activated factor X. Furthermore, compounds 1, 2, and 4 inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these potential in vitro antiplatelet activities, compounds 1, 2, and 4 showed enhanced antithrombotic effects in an in vivo pulmonary embolism and arterial thrombosis model. Compounds 1, 2, and 4 also elicited anticoagulant effects in mice. Collectively, this study may serve as the groundwork for commercializing SSM or compounds 1, 2, and 4 as functional food components for the prevention and treatment of pathogenic conditions and serve as new scaffolds for the development of anticoagulants.