Reduction of NF-κB signals in platelets and prolongation of platelet plug formation against high shear flow in whole blood on human subject by Columbianadin

Chih Wei Hsia, Chih Hao Yang, Joen Rong Sheu, Chih Hsuan Hsia, Cheng Lin Tsai, Wei Chieh Huang, Ting Yu Chen, Periyakali Saravana Bhavan, Yi Chang

Research output: Contribution to journalArticlepeer-review

Abstract

Myocardial infarction and cerebral ischemic stroke during the process of arterial thrombosis are prominently causes of death worldwide. Platelets are anucleated cells and play a critical factor in these diseases. Columbianadin (CBN), a coumarin derivative from plants, inhibits effective platelet activation. In this study, platelet function analysis revealed that the closure time of the platelet plug in human whole blood significantly prolonged by CBN, whereas CBN did not pointedly prolong the bleeding time in mice. BAY11-7082 (an inhibitor of IκB kinase) and MG-132 (an inhibitor of proteasome) inhibited collagen-stimulated platelet aggregation and ATP-release in human platelets, BAY11-7082 exhibited a higher potency than MG-132. Moreover, CBN markedly reduced NF-κB activation (e.g., IκBα and p65 phosphorylation) and reversed IκBα degradation in activated platelets. We investigated intercellular signaling events between mitogen-activated protein kinases and NF-κB, and found that BAY11-7082 abolished JNK1/2 and ERK1/2 phosphorylation. Interestingly, SP600125 (an inhibitor of JNK) but not PD98059 (an inhibitor of ERK) had no effect in NF-κB activation in activated platelets. Moreover, CBN but not BAY11-7082 significantly reduced hydroxyl radical (HO) formation in platelets. Therefore, we propose that CBN inhibits NF-κB activation in human platelets and could present a potent clinical treatment for thromboembolic diseases.

Original languageEnglish
Article number7323
Pages (from-to)1-15
Number of pages15
JournalApplied Sciences (Switzerland)
Volume10
Issue number20
DOIs
Publication statusPublished - Oct 2 2020

Keywords

  • Arterial thrombosis
  • Columbianadin
  • ERK1/2
  • Human platelets
  • Hydroxyl radical
  • JNK1/2
  • NF-κB

ASJC Scopus subject areas

  • Materials Science(all)
  • Instrumentation
  • Engineering(all)
  • Process Chemistry and Technology
  • Computer Science Applications
  • Fluid Flow and Transfer Processes

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