Comparison of the potency of pterostilbene with nf-κb inhibitors in platelet activation: Mutual activation by akt-nf-κb signaling in human platelets

Chih Hsuan Hsia, Wei Chieh Huang, Chih Hao Yang, Chih Hsuan Hsia, Thanasekaran Jayakumar, Periyakali Saravana Bhavan, Joen Rong Sheu, Kuan Rau Chiou

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Myocardial infarction and cerebral ischemic stroke are prominent causes of death worldwide. Platelets play major roles in these diseases, although they are anucleated cells, but also express the NF-κB. Pterostilbene (PTE) possesses some intriguing pharmacological properties, including the capacity to inhibit platelet activation. We investigated the inhibitory role of PTE in NF-κB-mediated signal events and compared the relative potency with that of classical NF-κB inhibitors. PTE and IκB kinase (IKK) inhibitor, BAY11-7082, and proteasome inhibitor, Ro106-9920, inhibited platelet aggregation; the activity of BAY11-7082 and PTE were similar, but Ro106-9920 was weak in this reaction. PTE and BAY11-7082 diminished NF-κB signaling molecules, including IKK, IκBα, and p65 phosphorylation, and reversed IκBα degradation. However, Ro106-9920 was only effective in diminishing p65 phosphorylation and reversing IκBα degradation. In investigating the role of Akt and NF-κB in cell signaling events, MK-2206 (an inhibitor of Akt) markedly abolished IKK and p65 phosphorylation; BAY11-7082 also reduced Akt phosphorylation. PTE exhibited more potent activity in vivo than did BAY11-7082 in acute pulmonary thromboembolism. In conclusion, we identified a distinctive activation pathway of NF-κB and Akt involved in PTE-mediated antiplatelet aggregation, and PTE demonstrated powerful activity as a prophylactic and as clinical therapy for cardiovascular diseases.

Original languageEnglish
Article number6149
JournalApplied Sciences (Switzerland)
Volume11
Issue number13
DOIs
Publication statusPublished - Jul 1 2021

Keywords

  • Akt
  • Arterial thrombosis
  • Human platelets
  • NF-κB
  • Pterostilbene

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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