Novel therapeutic agent against platelet activation in vitro and arterial thrombosis in vivo by morin hydrate

Chih Wei Hsia, Ming Ping Wu, Marappan Velusamy, Chih Hsuan Hsia, Duen Suey Chou, Cheng Lin Tsai, Chia Yuan Hsu, Thanasekaran Jayakumar, Chi Li Chung, Joen Rong Sheu

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

Morin hydrate, a bioactive flavonoid, has been proven to prevent inflammation and apoptosis of cells. Flavonoids can reduce the risk of cardiovascular diseases, in which platelet activation plays a major role. This study investigated the effect of morin hydrate on platelet activation in vitro and in vivo. Morin hydrate markedly inhibited platelet aggregation stimulated by collagen in human platelets but not that stimulated by other agonists. In collagen-activated platelets, morin hydrate inhibited adenosine triphosphate (ATP) release; intracellular Ca2+ mobilization; P-selectin expression; and phosphorylation of phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), and Akt. In mitogen-activated protein kinase (MAPK) activation, morin hydrate evidently diminished ERK2 or JNK1 activation, except for p38 MAPK. Additionally, morin hydrate markedly reduced the OH· signals in platelet suspensions but not in the cell-free system (Fenton reaction solution). Moreover, morin hydrate substantially increased the occlusion time of thrombotic platelet plug formation but had no effect on bleeding time in mice. In conclusion, morin hydrate crucially inhibits platelet activation through inhibition of the PLCγ2–PKC cascade and subsequent suppression of Akt and MAPK activation, thereby ultimately inhibiting platelet aggregation. Therefore, this paper suggests that morin hydrate constitutes a novel and potential natural therapeutic product for preventing or treating thromboembolic disorders.
原文英語
文章編號2386
期刊International Journal of Molecular Sciences
19
發行號8
DOIs
出版狀態已發佈 - 八月 13 2018

指紋

thrombosis
Platelet Activation
Platelets
platelets
Hydrates
hydrates
Thrombosis
Chemical activation
activation
Blood Platelets
proteins
Proteins
Flavonoids
Therapeutics
collagens
Mitogen-Activated Protein Kinases
Platelet Aggregation
Collagen
Agglomeration
In Vitro Techniques

ASJC Scopus subject areas

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry

引用此文

Novel therapeutic agent against platelet activation in vitro and arterial thrombosis in vivo by morin hydrate. / Hsia, Chih Wei; Wu, Ming Ping; Velusamy, Marappan; Hsia, Chih Hsuan; Chou, Duen Suey; Tsai, Cheng Lin; Hsu, Chia Yuan; Jayakumar, Thanasekaran; Chung, Chi Li; Sheu, Joen Rong.

於: International Journal of Molecular Sciences, 卷 19, 編號 8, 2386, 13.08.2018.

研究成果: 雜誌貢獻文章

Hsia, Chih Wei ; Wu, Ming Ping ; Velusamy, Marappan ; Hsia, Chih Hsuan ; Chou, Duen Suey ; Tsai, Cheng Lin ; Hsu, Chia Yuan ; Jayakumar, Thanasekaran ; Chung, Chi Li ; Sheu, Joen Rong. / Novel therapeutic agent against platelet activation in vitro and arterial thrombosis in vivo by morin hydrate. 於: International Journal of Molecular Sciences. 2018 ; 卷 19, 編號 8.
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abstract = "Morin hydrate, a bioactive flavonoid, has been proven to prevent inflammation and apoptosis of cells. Flavonoids can reduce the risk of cardiovascular diseases, in which platelet activation plays a major role. This study investigated the effect of morin hydrate on platelet activation in vitro and in vivo. Morin hydrate markedly inhibited platelet aggregation stimulated by collagen in human platelets but not that stimulated by other agonists. In collagen-activated platelets, morin hydrate inhibited adenosine triphosphate (ATP) release; intracellular Ca2+ mobilization; P-selectin expression; and phosphorylation of phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), and Akt. In mitogen-activated protein kinase (MAPK) activation, morin hydrate evidently diminished ERK2 or JNK1 activation, except for p38 MAPK. Additionally, morin hydrate markedly reduced the OH· signals in platelet suspensions but not in the cell-free system (Fenton reaction solution). Moreover, morin hydrate substantially increased the occlusion time of thrombotic platelet plug formation but had no effect on bleeding time in mice. In conclusion, morin hydrate crucially inhibits platelet activation through inhibition of the PLCγ2–PKC cascade and subsequent suppression of Akt and MAPK activation, thereby ultimately inhibiting platelet aggregation. Therefore, this paper suggests that morin hydrate constitutes a novel and potential natural therapeutic product for preventing or treating thromboembolic disorders.",
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T1 - Novel therapeutic agent against platelet activation in vitro and arterial thrombosis in vivo by morin hydrate

AU - Hsia, Chih Wei

AU - Wu, Ming Ping

AU - Velusamy, Marappan

AU - Hsia, Chih Hsuan

AU - Chou, Duen Suey

AU - Tsai, Cheng Lin

AU - Hsu, Chia Yuan

AU - Jayakumar, Thanasekaran

AU - Chung, Chi Li

AU - Sheu, Joen Rong

PY - 2018/8/13

Y1 - 2018/8/13

N2 - Morin hydrate, a bioactive flavonoid, has been proven to prevent inflammation and apoptosis of cells. Flavonoids can reduce the risk of cardiovascular diseases, in which platelet activation plays a major role. This study investigated the effect of morin hydrate on platelet activation in vitro and in vivo. Morin hydrate markedly inhibited platelet aggregation stimulated by collagen in human platelets but not that stimulated by other agonists. In collagen-activated platelets, morin hydrate inhibited adenosine triphosphate (ATP) release; intracellular Ca2+ mobilization; P-selectin expression; and phosphorylation of phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), and Akt. In mitogen-activated protein kinase (MAPK) activation, morin hydrate evidently diminished ERK2 or JNK1 activation, except for p38 MAPK. Additionally, morin hydrate markedly reduced the OH· signals in platelet suspensions but not in the cell-free system (Fenton reaction solution). Moreover, morin hydrate substantially increased the occlusion time of thrombotic platelet plug formation but had no effect on bleeding time in mice. In conclusion, morin hydrate crucially inhibits platelet activation through inhibition of the PLCγ2–PKC cascade and subsequent suppression of Akt and MAPK activation, thereby ultimately inhibiting platelet aggregation. Therefore, this paper suggests that morin hydrate constitutes a novel and potential natural therapeutic product for preventing or treating thromboembolic disorders.

AB - Morin hydrate, a bioactive flavonoid, has been proven to prevent inflammation and apoptosis of cells. Flavonoids can reduce the risk of cardiovascular diseases, in which platelet activation plays a major role. This study investigated the effect of morin hydrate on platelet activation in vitro and in vivo. Morin hydrate markedly inhibited platelet aggregation stimulated by collagen in human platelets but not that stimulated by other agonists. In collagen-activated platelets, morin hydrate inhibited adenosine triphosphate (ATP) release; intracellular Ca2+ mobilization; P-selectin expression; and phosphorylation of phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), and Akt. In mitogen-activated protein kinase (MAPK) activation, morin hydrate evidently diminished ERK2 or JNK1 activation, except for p38 MAPK. Additionally, morin hydrate markedly reduced the OH· signals in platelet suspensions but not in the cell-free system (Fenton reaction solution). Moreover, morin hydrate substantially increased the occlusion time of thrombotic platelet plug formation but had no effect on bleeding time in mice. In conclusion, morin hydrate crucially inhibits platelet activation through inhibition of the PLCγ2–PKC cascade and subsequent suppression of Akt and MAPK activation, thereby ultimately inhibiting platelet aggregation. Therefore, this paper suggests that morin hydrate constitutes a novel and potential natural therapeutic product for preventing or treating thromboembolic disorders.

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KW - Adenosine Triphosphate/metabolism

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KW - Platelet Activation/drug effects

KW - Proto-Oncogene Proteins c-akt/metabolism

KW - Mice, Inbred ICR

KW - Calcium/metabolism

KW - Protein Kinase C/metabolism

KW - Animals

KW - Mitogen-Activated Protein Kinases/metabolism

KW - Platelet Aggregation/drug effects

KW - Mice

KW - Flavonoids/chemistry

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DO - 10.3390/ijms19082386

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