Specific inhibiting effects of Ilexonin A on von Willebrand factor-dependent platelet aggregation under high shear rate
摘要Background Ilexonin A (IA), purified from the Chinese herbal medicine Maodongqing (Ilex pubescens Hook, et Am) has been commonly used in south China to treat thrombotic disorders. In this study, we aimed to study the inhibiting effects and mechanism of lA on von Willebrand factor (vWF)-dependent high shear-induced platelet aggregation. Methods vWF-dependent high shear (10 800 s-1) induced aggregation of platelets obtained from normal donors in the presence or absence of lA was measured by a modified cone-plate viscometer and shear-induced vWF binding was measured by quantitative flowcytometry with monoclonal antibody known to bind exclusively to the C-terminal domain of vWF (LJ-C3) directly labeled with fluorescein isothiocyanate (FITC). P-selectin surface expression was also measured by a similar method with FITC conjugated anti-P-selectin monoclonal antibody (WGA1).Results Shear-induced platelet aggregation was inhibited by IA in a dose-dependent manner. The extent of aggregation decreased from (78.6±4.6)% in the absence of lA to (36.5±2.1 )% in the presence of lA (3.3 mmol/L) (P<0.0001, n=9) with a high shear rate of 10800 s-1. vWF binding and P-selectin expression were also inhibited by lA in a dose dependent manner. The number of binding FITC-LJ-C3 molecules increased after exposure of platelet-rich plasma to a high shear rate of 10 800 s-1 for 6 minutes, but this shear-induced increased binding platelet surface vWF molecules and P-selectin expression can be decreased in the presence of IA.Conclusion vWF binding and vWF mediated platelet activation, aggregation occurring under high shear rate were inhibited by IA. lA may be a unique antithrombotic drug inhibiting the vWF-GP Ib α interaction, and may thus facilitate drug design targeting arterial thrombosis.
更多相关知识
- 浏览87
- 被引8
- 下载0

相似文献
- 中文期刊
- 外文期刊
- 学位论文
- 会议论文