Inhibition of platelet aggregation by curdione from Curcuma wenyujin essential Oil

抗血栓 化学 血小板 弹性蛋白酶 凝血酶 体内 二磷酸腺苷 花生四烯酸 药理学 细胞内 生物化学 血小板聚集 体外 医学 生物 免疫学 内科学 生物技术
作者
Xia Qin,Xiu Wang,Donghui Xu,Xiao-Huan Chen,Feihu Chen
出处
期刊:Thrombosis Research [Elsevier]
卷期号:130 (3): 409-414 被引量:74
标识
DOI:10.1016/j.thromres.2012.04.005
摘要

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.
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