α-Naphthoflavone, a potent antiplatelet flavonoid, is mediated through inhibition of phospholipase C activity and stimulation of cyclic GMP formation

George Hsiao, Ching Yi Chang, Ming Yi Shen, Duen Suey Chou, Shu Hw Tzeng, Tzeng-Fu Chen, Joen Rong Sheu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The aim of this study was to systematically examine the inhibitory mechanisms of the flavonoid α-naphthoflavone (α-NF) in platelet activation. In this study, α-NF concentration dependently (5-20 μM) inhibited platelet aggregation stimulated by agonists. α-NF (5 and 10 μM) inhibited intracellular Ca2+ mobilization, phosphoinositide breakdown, and thromboxane A2 formation stimulated by collagen (1 μg/mL) in human platelets. In addition, α-NF (5 and 10 μM) markedly increased levels of cyclic GMP and cyclic GMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser157 phosphorylation. Rapid phosphorylation of a platelet protein of Mr 47 000 (P47), a marker of protein kinase C activation, was triggered by phorbol-12,13-dibutyrate (60 nM). This phosphorylation was markedly inhibited by α-NF (5 and 10 μM). However, α-NF (5 and 10 μM) did not reduce the electron spin resonance (ESR) signal intensity of hydroxyl radicals in collagen (1 μg/mL)-activated platelets. These results indicate that the antiplatelet activity of α-NF may be involved in the following pathways. (1) α-NF may inhibit the activation of phospholipase C, followed by inhibition of phosphoinositide breakdown, protein kinase C activation, and thromboxane A2 formation, thereby leading to inhibition of intracellular Ca2+ mobilization. (2) α-NF also activated the formation of cyclic GMP, resulting in inhibition of platelet aggregation. These results strongly indicate that α-NF appears to represent a novel and potent antiplatelet agent for treatment of arterial thromboembolism.

Original languageEnglish
Pages (from-to)5179-5186
Number of pages8
JournalJournal of Agricultural and Food Chemistry
Volume53
Issue number13
DOIs
Publication statusPublished - Jun 29 2005

Fingerprint

cyclic GMP
phospholipase C
Cyclic GMP
Type C Phospholipases
Platelets
Flavonoids
phosphorylation
Thromboxane A2
thromboxanes
flavonoids
Blood Platelets
platelet aggregation
Phosphorylation
protein kinase C
Phosphatidylinositols
Platelet Aggregation
Protein Kinase C
collagen
Collagen
Chemical activation

Keywords

  • α-Naphthoflavone
  • Cyclic GMP
  • Platelet aggregation
  • Protein kinase C
  • Vasodilator-stimulated phosphoprotein

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Food Science
  • Chemistry (miscellaneous)

Cite this

α-Naphthoflavone, a potent antiplatelet flavonoid, is mediated through inhibition of phospholipase C activity and stimulation of cyclic GMP formation. / Hsiao, George; Chang, Ching Yi; Shen, Ming Yi; Chou, Duen Suey; Tzeng, Shu Hw; Chen, Tzeng-Fu; Sheu, Joen Rong.

In: Journal of Agricultural and Food Chemistry, Vol. 53, No. 13, 29.06.2005, p. 5179-5186.

Research output: Contribution to journalArticle

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abstract = "The aim of this study was to systematically examine the inhibitory mechanisms of the flavonoid α-naphthoflavone (α-NF) in platelet activation. In this study, α-NF concentration dependently (5-20 μM) inhibited platelet aggregation stimulated by agonists. α-NF (5 and 10 μM) inhibited intracellular Ca2+ mobilization, phosphoinositide breakdown, and thromboxane A2 formation stimulated by collagen (1 μg/mL) in human platelets. In addition, α-NF (5 and 10 μM) markedly increased levels of cyclic GMP and cyclic GMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser157 phosphorylation. Rapid phosphorylation of a platelet protein of Mr 47 000 (P47), a marker of protein kinase C activation, was triggered by phorbol-12,13-dibutyrate (60 nM). This phosphorylation was markedly inhibited by α-NF (5 and 10 μM). However, α-NF (5 and 10 μM) did not reduce the electron spin resonance (ESR) signal intensity of hydroxyl radicals in collagen (1 μg/mL)-activated platelets. These results indicate that the antiplatelet activity of α-NF may be involved in the following pathways. (1) α-NF may inhibit the activation of phospholipase C, followed by inhibition of phosphoinositide breakdown, protein kinase C activation, and thromboxane A2 formation, thereby leading to inhibition of intracellular Ca2+ mobilization. (2) α-NF also activated the formation of cyclic GMP, resulting in inhibition of platelet aggregation. These results strongly indicate that α-NF appears to represent a novel and potent antiplatelet agent for treatment of arterial thromboembolism.",
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T1 - α-Naphthoflavone, a potent antiplatelet flavonoid, is mediated through inhibition of phospholipase C activity and stimulation of cyclic GMP formation

AU - Hsiao, George

AU - Chang, Ching Yi

AU - Shen, Ming Yi

AU - Chou, Duen Suey

AU - Tzeng, Shu Hw

AU - Chen, Tzeng-Fu

AU - Sheu, Joen Rong

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N2 - The aim of this study was to systematically examine the inhibitory mechanisms of the flavonoid α-naphthoflavone (α-NF) in platelet activation. In this study, α-NF concentration dependently (5-20 μM) inhibited platelet aggregation stimulated by agonists. α-NF (5 and 10 μM) inhibited intracellular Ca2+ mobilization, phosphoinositide breakdown, and thromboxane A2 formation stimulated by collagen (1 μg/mL) in human platelets. In addition, α-NF (5 and 10 μM) markedly increased levels of cyclic GMP and cyclic GMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser157 phosphorylation. Rapid phosphorylation of a platelet protein of Mr 47 000 (P47), a marker of protein kinase C activation, was triggered by phorbol-12,13-dibutyrate (60 nM). This phosphorylation was markedly inhibited by α-NF (5 and 10 μM). However, α-NF (5 and 10 μM) did not reduce the electron spin resonance (ESR) signal intensity of hydroxyl radicals in collagen (1 μg/mL)-activated platelets. These results indicate that the antiplatelet activity of α-NF may be involved in the following pathways. (1) α-NF may inhibit the activation of phospholipase C, followed by inhibition of phosphoinositide breakdown, protein kinase C activation, and thromboxane A2 formation, thereby leading to inhibition of intracellular Ca2+ mobilization. (2) α-NF also activated the formation of cyclic GMP, resulting in inhibition of platelet aggregation. These results strongly indicate that α-NF appears to represent a novel and potent antiplatelet agent for treatment of arterial thromboembolism.

AB - The aim of this study was to systematically examine the inhibitory mechanisms of the flavonoid α-naphthoflavone (α-NF) in platelet activation. In this study, α-NF concentration dependently (5-20 μM) inhibited platelet aggregation stimulated by agonists. α-NF (5 and 10 μM) inhibited intracellular Ca2+ mobilization, phosphoinositide breakdown, and thromboxane A2 formation stimulated by collagen (1 μg/mL) in human platelets. In addition, α-NF (5 and 10 μM) markedly increased levels of cyclic GMP and cyclic GMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser157 phosphorylation. Rapid phosphorylation of a platelet protein of Mr 47 000 (P47), a marker of protein kinase C activation, was triggered by phorbol-12,13-dibutyrate (60 nM). This phosphorylation was markedly inhibited by α-NF (5 and 10 μM). However, α-NF (5 and 10 μM) did not reduce the electron spin resonance (ESR) signal intensity of hydroxyl radicals in collagen (1 μg/mL)-activated platelets. These results indicate that the antiplatelet activity of α-NF may be involved in the following pathways. (1) α-NF may inhibit the activation of phospholipase C, followed by inhibition of phosphoinositide breakdown, protein kinase C activation, and thromboxane A2 formation, thereby leading to inhibition of intracellular Ca2+ mobilization. (2) α-NF also activated the formation of cyclic GMP, resulting in inhibition of platelet aggregation. These results strongly indicate that α-NF appears to represent a novel and potent antiplatelet agent for treatment of arterial thromboembolism.

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