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

被引:10
作者
Hsia, Chih-Wei [1 ]
Wu, Ming-Ping [1 ,2 ]
Velusamy, Marappan [3 ]
Hsia, Chih-Hsuan [1 ]
Chou, Duen-Suey [4 ]
Tsai, Cheng-Lin [5 ]
Hsu, Chia-Yuan [1 ]
Jayakumar, Thanasekaran [1 ,4 ]
Chung, Chi-Li [6 ]
Sheu, Joen-Rong [1 ,4 ]
机构
[1] Taipei Med Univ, Grad Inst Med Sci, Coll Med, Taipei 110, Taiwan
[2] Chi Mei Med Ctr, Dept Obstet & Gynecol, Tainan 710, Taiwan
[3] North Eastern Hill Univ, Dept Chem, Shillong 793022, Meghalaya, India
[4] Taipei Med Univ, Sch Med, Dept Pharmacol, Coll Med, Taipei 110, Taiwan
[5] Taipei Med Univ, Coll Nutr, Grad Inst Metab & Obes Sci, Taipei 110, Taiwan
[6] Taipei Med Univ Hosp, Div Pulm Med, Dept Internal Med, Taipei 110, Taiwan
关键词
bleeding time; flavonoid; morin hydrate; OH<bold>center dot</bold> free radical; platelet activation; protein kinase; thromboembolism; MAP KINASE; EX-VIVO; COLLAGEN; GPVI; AGONIST; AGGREGATION; INHIBITION; MECHANISMS; ROLES; AKT;
D O I
10.3390/ijms19082386
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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 C gamma 2 (PLC gamma 2), 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 center dot 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 PLC gamma 2-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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页数:15
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