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Open AccessArticle

Novel Therapeutic Agent against Platelet Activation In Vitro and Arterial Thrombosis In Vivo by Morin Hydrate

1
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
2
Department of Obstetrics and Gynecology, Chi-Mei Medical Center, Tainan 710, Taiwan
3
Department of Chemistry, North Eastern Hill University, Shillong 793022, India
4
Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
5
Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 110, Taiwan
6
Division of Pulmonary Medicine, Department of Internal Medical, Taipei Medical University Hospital, Taipei 110, Taiwan
*
Authors to whom correspondence should be addressed.
All the authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(8), 2386; https://doi.org/10.3390/ijms19082386
Received: 31 July 2018 / Revised: 10 August 2018 / Accepted: 13 August 2018 / Published: 13 August 2018
(This article belongs to the Special Issue Plant Natural Products for Human Health)
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. View Full-Text
Keywords: bleeding time; flavonoid; morin hydrate; OH· free radical; platelet activation; protein kinase; thromboembolism bleeding time; flavonoid; morin hydrate; OH· free radical; platelet activation; protein kinase; thromboembolism
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Hsia, C.-W.; Wu, M.-P.; Velusamy, M.; Hsia, C.-H.; Chou, D.-S.; Tsai, C.-L.; Hsu, C.-Y.; Jayakumar, T.; Chung, C.-L.; Sheu, J.-R. Novel Therapeutic Agent against Platelet Activation In Vitro and Arterial Thrombosis In Vivo by Morin Hydrate. Int. J. Mol. Sci. 2018, 19, 2386.

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