The antithrombotic agent pterostilbene interferes with integrin αIIbβ3-mediated inside-out and outside-in signals in human platelets

Wei Chieh Huang, Kao Chang Lin, Chih Hsuan Hsia, Chih Hsuan Hsia, Ting Yu Chen, Periyakali Saravana Bhavan, Joen Rong Sheu, Shaw Min Hou

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Platelets play a crucial role in the physiology of primary hemostasis and pathological processes such as arterial thrombosis; thus, developing a therapeutic target that prevents platelet activation can reduce arterial thrombosis. Pterostilbene (PTE) has remarkable pharmacological activities, including anticancer and neuroprotection. Few studies have reported the effects of pterostilbene on platelet activation. Thus, we examined the inhibitory mechanisms of pterostilbene in human platelets and its role in vascular thrombosis prevention in mice. At low concentrations (2–8 μM), pterostilbene strongly inhibited collagen-induced platelet aggregation. Furthermore, pterostilbene markedly diminished Lyn, Fyn, and Syk phosphorylation and hydroxyl radical formation stimulated by collagen. Moreover, PTE directly hindered integrin αIIbβ3 activation through interfering with PAC-1 binding stimulated by collagen. In addition, pterostilbene affected integrin αIIbβ3-mediated outside-in signaling, such as integrin β3, Src, and FAK phosphorylation, and reduced the number of adherent platelets and the single platelet spreading area on immobilized fibrinogen as well as thrombin-stimulated fibrin clot retraction. Furthermore, pterostilbene sub-stantially prolonged the occlusion time of thrombotic platelet plug formation in mice. This study demonstrated that pterostilbene exhibits a strong activity against platelet activation through the inhibition of integrin αIIbβ3-mediated inside-out and outside-in signaling, suggesting that pterostilbene can serve as a therapeutic agent for thromboembolic disorders.

Original languageEnglish
Article number3643
JournalInternational journal of molecular sciences
Volume22
Issue number7
DOIs
Publication statusPublished - Apr 1 2021

Keywords

  • Arterial thrombosis
  • Hydroxyl radicals
  • Integrin αIIbβ3
  • Platelet aggregation
  • Pterostilbene
  • Resveratrol derivative

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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