Ent-16β,17-dihydroxy-kauran-19-oic acid, a kaurane diterpene acid from Siegesbeckia pubescens, presents antiplatelet and antithrombotic effects in rats
Ent-16β,17-dihydroxy-kauran-19-oic acid, a kaurane diterpene acid from Siegesbeckia pubescens, presents antiplatelet and antithrombotic effects in rats
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DOI：
10.1016/j.phymed.2011.01.024
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发表时间：
2011-07-15
期刊：
影响因子：
7.9
通讯作者：
Cai, Y. L.
中科院分区：
文献类型：
--
作者：
Wang, J. P.;Xu, H. X.;Cai, Y. L.
采用不同的方法研究了从毛Siegesbeckia pubescens中分离得到的ent-16 β，17-dihydroxy-kauran-19-oic acid（DDKA）的体内外抗血小板和血栓形成作用。我们在动静脉分流模型中检测了DDKA的抗血栓活性。体外观察DDKA对二磷酸腺苷（ADP）、凝血酶、花生四烯酸诱导的大鼠血小板聚集的影响。我们还通过静脉给药5天后测量凝血参数来评估其出血副作用，并研究了这些活性的潜在机制。在体内，DDKA显著降低动静脉分流模型中的血栓重量。DDKA还可增加同一模型大鼠血浆cAMP水平。DDKA连续5天静脉给药后，PT和APTT明显延长。在体外，DDKA预处理洗涤的大鼠血小板可显著抑制各种激动剂刺激的血小板聚集，并引起ADP激活的血小板cAMP水平升高。这些结果支持我们的假设，DDKA具有抗血小板和抗血栓形成的活动。其作用机制可能与抗凝作用和cAMP诱导有关。(C)2011年Elsevier GmbH。All rights reserved.
The antiplatelet and antithrombotic effects of ent-16 beta,17-dihydroxy-kauran-19-oic acid (DDKA) isolated from Siegesbeckia pubescens were investigated with different methods both in vitro and in vivo. We tested the antithrombotic activity of DDKA in arterio-venous shunt model. The effects of DDKA on adenosine diphosphate (ADP)-, Thrombin-, Arachidonic acid-induced rat platelets aggregation were tested in vitro. We also assessed its bleeding side effect by measuring coagulation parameters after intravenous administration for 5 days and investigated the potential mechanisms underlying such activities. In vivo, DDKA significantly reduced thrombus weight in the model of arterio-venous shunt. Meanwhile, DDKA increased plasma cAMP level determined by radioimmunoassay in the same model. Notably, DDKA prolonged PT and APTT in rats after intravenous administration DDKA for successive 5 clays. In vitro, pretreatment with DDKA on washed rat platelets significantly inhibited various agonists stimulated platelet aggregation and caused an increase in cAMP level in platelets activated by ADP. These findings support our hypothesis that DDKA possesses antiplatelet and antithrombotic activities. The mechanisms underlying such activities may involve the anticoagulatory effect and cAMP induction. (C) 2011 Elsevier GmbH. All rights reserved.