Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui, China.
Thromb Res. 2012 Sep;130(3):409-14. doi: 10.1016/j.thromres.2012.04.005. Epub 2012 May 3.
Curdione, one of the major sesquiterpene compounds from Rhizoma Curcumae, has been shown to exhibit multiple bioactive properties. In this study, we investigated the anti-platelet aggregation and antithrombotic activities of curdione with different methods both in vitro and in vivo. The purpose of the study was to explore an inhibitor of platelet aggregation, which promised to be a preventive or therapeutic agent for various vascular diseases.
Curdione was isolated from the essential oil of Curcuma wenyujin using the silica gel column chromatography method. The effects of curdione on human platelet aggregation induced by thrombin (0.3 U/ml), platelet-activating factor (PAF, 0.375 μg/ml), adenosine diphosphate (ADP, 10 μM) and arachidonic acid (AA, 0.1mg/ml) were tested in vitro, and the potential mechanisms underlying such activities were investigated. We also tested the antithrombotic effect of curdione in a tail thrombosis model.
Curdione preferentially inhibited PAF- and thrombin- induced platelet aggregation in a concentration-dependent manner (IC(50): 60-80 μM), whereas much higher concentrations of curdione were required to inhibit platelet aggregation induced by ADP and AA. Curdione also inhibited P-selectin expression in PAF-activated platelets. Moreover, curdione caused an increase in cAMP levels and attenuated intracellular Ca(2+) mobilization in PAF-activated platelets. In vivo, we also found that curdione showed significant antithrombotic activity. Therefore, we conclude that the inhibitory mechanism of curdione on platelet aggregation may increase cAMP levels and subsequently inhibit intracellular Ca(2+) mobilization. Furthermore, the effect observed in the tail thrombosis model might be explained completely by increased vasodilation. These results indicate that curdione may be one of the main bioactive constituents in Rhizoma Curcumae that removes blood stasis.
莪术烯是姜黄根茎中的一种主要倍半萜化合物，已显示出多种生物活性。在这项研究中，我们使用不同的方法在体外和体内研究了莪术烯的抗血小板聚集和抗血栓形成活性。研究的目的是探索一种血小板聚集抑制剂，有望成为各种血管疾病的预防或治疗药物。
莪术烯是使用硅胶柱层析法从温郁金挥发油中分离得到的。在体外测试了莪术烯对凝血酶（0.3 U/ml）、血小板活化因子（PAF，0.375 μg/ml）、二磷酸腺苷（ADP，10 μM）和花生四烯酸（AA，0.1mg/ml）诱导的人血小板聚集的影响，并研究了这种活性的潜在机制。我们还在尾血栓模型中测试了莪术烯的抗血栓形成作用。
莪术烯优先以浓度依赖性方式抑制 PAF 和凝血酶诱导的血小板聚集（IC50：60-80 μM），而抑制 ADP 和 AA 诱导的血小板聚集则需要更高浓度的莪术烯。莪术烯还抑制 PAF 激活血小板中的 P-选择素表达。此外，莪术烯导致 cAMP 水平升高，并减弱 PAF 激活血小板中的细胞内 Ca2+动员。在体内，我们还发现莪术烯具有显著的抗血栓形成活性。因此，我们得出结论，莪术烯抑制血小板聚集的机制可能是通过增加 cAMP 水平，进而抑制细胞内 Ca2+动员。此外，尾血栓模型中观察到的效果可能完全可以通过增加血管扩张来解释。这些结果表明，莪术烯可能是姜黄根茎中去除血瘀的主要生物活性成分之一。
