Potent antiplatelet activity of sesamol in an in vitro and in vivo model: Pivotal roles of cyclic AMP and p38 mitogen-activated protein kinase

Chao C. Chang, Wan-Jung Lu, Cheng-Wen Chiang, Thanasekaran Jayakumar, Eng T. Ong, George Hsiao, Tsorng H. Fong, Duen S. Chou, Joen R. Sheu

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Sesamol is a potent phenolic antioxidant which possesses antimutagenic, antihepatotoxic and antiaging properties. Platelet activation is relevant to a variety of acute thrombotic events and coronary heart diseases. There have been few studies on the effect of sesamol on platelets. Therefore, the aim of this study was to systematically examine the detailed mechanisms of sesamol in preventing platelet activation in vitro and in vivo. Sesamol (2.5-5 μM) exhibited more potent activity of inhibiting platelet aggregation stimulated by collagen than other agonists. Sesamol inhibited collagen-stimulated platelet activation accompanied by [Ca2+]i mobilization, thromboxane A2 (TxA2) formation, and phospholipase C (PLC)γ2, protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) phosphorylation in washed platelets. Sesamol markedly increased cAMP and cGMP levels, endothelial nitric oxide synthase (eNOS) expression and NO release, as well as vasodilator-stimulated phosphoprotein (VASP) phosphorylation. SQ22536, an inhibitor of adenylate cyclase, markedly reversed the sesamol-mediated inhibitory effects on platelet aggregation and p38 MAPK phosphorylation, and sesamol-mediated stimulatory effects on VASP and eNOS phosphorylation, and NO release. Sesamol also reduced hydroxyl radical (OH{filled circle}) formation in platelets. In an in vivo study, sesamol (5 mg/kg) significantly prolonged platelet plug formation in mice. The most important findings of this study demonstrate for the first time that sesamol possesses potent antiplatelet activity, which may involve activation of the cAMP-eNOS/NO-cGMP pathway, resulting in inhibition of the PLCγ2-PKC-p38 MAPK-TxA2 cascade, and, finally, inhibition of platelet aggregation. Sesamol treatment may represent a novel approach to lowering the risk of or improving function in thromboembolism-related disorders.

Original languageEnglish
Pages (from-to)1214-1221
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume21
Issue number12
DOIs
Publication statusPublished - Dec 2010

Keywords

  • Cyclic AMP
  • Nitric oxide
  • P38 MAPK
  • Platelet activation
  • PLCγ2
  • Sesamol

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Fingerprint Dive into the research topics of 'Potent antiplatelet activity of sesamol in an in vitro and in vivo model: Pivotal roles of cyclic AMP and p38 mitogen-activated protein kinase'. Together they form a unique fingerprint.

  • Cite this