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.
Funder
Ministry of Science and Technology, Taiwan
Taipei Medical University-Shuang Ho Hospital
Taipei Medical University
Subject
Fluid Flow and Transfer Processes,Computer Science Applications,Process Chemistry and Technology,General Engineering,Instrumentation,General Materials Science
Cited by
5 articles.
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