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

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2 Citations (Scopus)

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.

Original languageEnglish
Article number2386
JournalInternational Journal of Molecular Sciences
Volume19
Issue number8
DOIs
Publication statusPublished - Aug 13 2018

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Keywords

  • Bleeding time
  • Flavonoid
  • Free radical
  • Morin hydrate
  • OH
  • Platelet activation
  • Protein kinase
  • Thromboembolism
  • P-Selectin/metabolism
  • Blood Platelets/cytology
  • Humans
  • Adenosine Triphosphate/metabolism
  • Male
  • Thrombosis/drug therapy
  • Platelet Activation/drug effects
  • Proto-Oncogene Proteins c-akt/metabolism
  • Mice, Inbred ICR
  • Calcium/metabolism
  • Protein Kinase C/metabolism
  • Animals
  • Mitogen-Activated Protein Kinases/metabolism
  • Platelet Aggregation/drug effects
  • Mice
  • Flavonoids/chemistry

ASJC Scopus subject areas

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

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