Inhibitory mechanisms of resveratrol in platelet activation

Pivotal roles of p38 MAPK and NO/cyclic GMP

Ming Y. Shen, George Hsiao, Chang L. Liu, Tsorng H. Fong, Kuang H. Lin, Duen S. Chou, Joen R. Sheu

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Resveratrol has been reported to have antiplatelet activity; however, the detailed mechanisms have not yet been resolved. This study aimed to systematically examine the detailed mechanisms of resveratrol in the prevention of platelet activation in vitro and in vivo. Resveratrol (0.05-0.25 μmol/l) showed stronger inhibition of platelet aggregation stimulated by collagen (1 μg/ml) than other agonists. Resveratrol (0.15 and 0.25 μmol/l) inhibited collagen-induced platelet activation accompanied by [Ca+2]i mobilization, thromboxane A2 (TxA2) formation, phosphoinositide breakdown, and protein kinase C (PKC) activation. Resveratrol markedly increased levels of NO/cyclic guanosine monophosphate (GMP), and cyclic GMP-induced vasodilator-stimulated phosphoprotein phosphorylation. Resveratrol markedly inhibited p38 mitogen-activated protein kinase (MAPK) but not Jun N-terminal kinase or extracellular signal-regulated kinase-2 phosphorylation in washed platelets. Resveratrol-reduced hydroxyl radical (OH-) formation in the electron spin resonance study. In an in vivo study, resveratrol (5 mg/kg) significantly prolonged platelet plug formation of mice. In conclusion, the main findings of this study suggest that the inhibitory effects of resveratrol possibly involve (i) inhibition of the p38 MAPK-cytosolic phospholipase A2-arachidonic acid-TxA2-[Ca+2]i cascade and (ii) activation of NO/cyclic GMP, resulting in inhibition of phospholipase C and/or PKC activation. Resveratrol is likely to exert significant protective effects in thromboembolic-related disorders by inhibiting platelet aggregation.

Original languageEnglish
Pages (from-to)475-485
Number of pages11
JournalBritish Journal of Haematology
Volume139
Issue number3
DOIs
Publication statusPublished - Nov 2007

Fingerprint

Cyclic GMP
Platelet Activation
p38 Mitogen-Activated Protein Kinases
Thromboxane A2
Platelet Aggregation
Protein Kinase C
Collagen
Blood Platelets
Phosphorylation
resveratrol
Cytosolic Phospholipases A2
1-Phosphatidylinositol 4-Kinase
Mitogen-Activated Protein Kinase 1
Electron Spin Resonance Spectroscopy
Type C Phospholipases
Arachidonic Acid
Hydroxyl Radical
Phosphotransferases

Keywords

  • Cyclic guanosine monophosphate
  • Hydroxyl radical
  • p38 mitogen-activated protein kinase
  • Platelet activation
  • Resveratrol

ASJC Scopus subject areas

  • Hematology

Cite this

Inhibitory mechanisms of resveratrol in platelet activation : Pivotal roles of p38 MAPK and NO/cyclic GMP. / Shen, Ming Y.; Hsiao, George; Liu, Chang L.; Fong, Tsorng H.; Lin, Kuang H.; Chou, Duen S.; Sheu, Joen R.

In: British Journal of Haematology, Vol. 139, No. 3, 11.2007, p. 475-485.

Research output: Contribution to journalArticle

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abstract = "Resveratrol has been reported to have antiplatelet activity; however, the detailed mechanisms have not yet been resolved. This study aimed to systematically examine the detailed mechanisms of resveratrol in the prevention of platelet activation in vitro and in vivo. Resveratrol (0.05-0.25 μmol/l) showed stronger inhibition of platelet aggregation stimulated by collagen (1 μg/ml) than other agonists. Resveratrol (0.15 and 0.25 μmol/l) inhibited collagen-induced platelet activation accompanied by [Ca+2]i mobilization, thromboxane A2 (TxA2) formation, phosphoinositide breakdown, and protein kinase C (PKC) activation. Resveratrol markedly increased levels of NO/cyclic guanosine monophosphate (GMP), and cyclic GMP-induced vasodilator-stimulated phosphoprotein phosphorylation. Resveratrol markedly inhibited p38 mitogen-activated protein kinase (MAPK) but not Jun N-terminal kinase or extracellular signal-regulated kinase-2 phosphorylation in washed platelets. Resveratrol-reduced hydroxyl radical (OH-) formation in the electron spin resonance study. In an in vivo study, resveratrol (5 mg/kg) significantly prolonged platelet plug formation of mice. In conclusion, the main findings of this study suggest that the inhibitory effects of resveratrol possibly involve (i) inhibition of the p38 MAPK-cytosolic phospholipase A2-arachidonic acid-TxA2-[Ca+2]i cascade and (ii) activation of NO/cyclic GMP, resulting in inhibition of phospholipase C and/or PKC activation. Resveratrol is likely to exert significant protective effects in thromboembolic-related disorders by inhibiting platelet aggregation.",
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AU - Hsiao, George

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AU - Fong, Tsorng H.

AU - Lin, Kuang H.

AU - Chou, Duen S.

AU - Sheu, Joen R.

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