Specific inhibiting effects of Ilexonin A on von Willebrand factor-dependent platelet aggregation under high shear rate

Min LI*, Wei Kang Wu, Liang LIU, Fu Long Liao, Yukito Shinohara, Shunnosuke Handa, Shinya Goto

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background. Ilexonin A (IA), purified from the Chinese herbal medicine Maodongqing (Ilex pubescens Hook, et Arn) has been commonly used in south China to treat thrombotic disorders. In this study, we aimed to study the inhibiting effects and mechanism of IA 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 IA 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 IA to (36.5 ±2.1)% in the presence of IA (3.3 mmol/L) (P <0.0001, n=9) with a high shear rate of 10 800 s-1. vWF binding and P-selectin expression were also inhibited by IA 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. IA may be a unique antithrombotic drug inhibiting the vWF-GP Ibα interaction, and may thus facilitate drug design targeting arterial thrombosis.

Original languageEnglish
Pages (from-to)241-246
Number of pages6
JournalChinese Medical Journal
Volume117
Issue number2
Publication statusPublished - Feb 2004

Scopus Subject Areas

  • Medicine(all)

User-Defined Keywords

  • High shear rate
  • Ilexonin A
  • P-selectin
  • Platelet aggregation
  • von Willebrand factor

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