-Naphthoflavone, a Potent Antiplatelet Flavonoid, Is Mediated through Inhibition of Phospholipase C Activity and Stimulation of Cycl
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- 作者：George Hsiao ; Ching-Yi Chang ; Ming-Yi Shen ; Duen-Suey Chou ; Shu-Hw Tzeng ; Tzeng-Fu Chen ; and Joen-Rong Sheu
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2005
- 出版时间：June 29, 2005
- 年：2005
- 卷：53
- 期：13
- 页码：5179 - 5186
- 全文大小：269K
- 年卷期：v.53,no.13(June 29, 2005)
- ISSN：1520-5118
文摘
The aim of this study was to systematically examine the inhibitory mechanisms of the flavonoid
-naphthoflavone (-NF) in platelet activation. In this study, -NF concentration dependently (5-20
M) inhibited platelet aggregation stimulated by agonists. -NF (5 and 10 M) inhibited intracellularCa2+ mobilization, phosphoinositide breakdown, and thromboxane A2 formation stimulated by collagen(1 g/mL) in human platelets. In addition, -NF (5 and 10 M) markedly increased levels of cyclicGMP 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-NF (5 and 10 M). However, -NF (5 and 10 M) did not reduce the electron spin resonance(ESR) signal intensity of hydroxyl radicals in collagen (1 g/mL)-activated platelets. These resultsindicate that the antiplatelet activity of -NF may be involved in the following pathways. (1) -NFmay 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 intracellularCa2+ mobilization. (2) -NF also activated the formation of cyclic GMP, resulting in inhibition of plateletaggregation. These results strongly indicate that -NF appears to represent a novel and potentantiplatelet agent for treatment of arterial thromboembolism.Keywords: -Naphthoflavone; platelet aggregation; protein kinase C; cyclic GMP; vasodilator-stimulatedphosphoprotein
-naphthoflavone (-NF) in platelet activation. In this study, -NF concentration dependently (5-20M) inhibited platelet aggregation stimulated by agonists. -NF (5 and 10 M) inhibited intracellularCa2+ mobilization, phosphoinositide breakdown, and thromboxane A2 formation stimulated by collagen(1 g/mL) in human platelets. In addition, -NF (5 and 10 M) markedly increased levels of cyclicGMP 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-NF (5 and 10 M). However, -NF (5 and 10 M) did not reduce the electron spin resonance(ESR) signal intensity of hydroxyl radicals in collagen (1 g/mL)-activated platelets. These resultsindicate that the antiplatelet activity of -NF may be involved in the following pathways. (1) -NFmay 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 intracellularCa2+ mobilization. (2) -NF also activated the formation of cyclic GMP, resulting in inhibition of plateletaggregation. These results strongly indicate that -NF appears to represent a novel and potentantiplatelet agent for treatment of arterial thromboembolism.Keywords: -Naphthoflavone; platelet aggregation; protein kinase C; cyclic GMP; vasodilator-stimulatedphosphoprotein© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |