TY - JOUR
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.
KW - Bleeding time
KW - Flavonoid
KW - Free radical
KW - Morin hydrate
KW - OH
KW - Platelet activation
KW - Protein kinase
KW - Thromboembolism
KW - P-Selectin/metabolism
KW - Blood Platelets/cytology
KW - Humans
KW - Adenosine Triphosphate/metabolism
KW - Male
KW - Thrombosis/drug therapy
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
UR - http://www.scopus.com/inward/record.url?scp=85052074007&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052074007&partnerID=8YFLogxK
U2 - 10.3390/ijms19082386
DO - 10.3390/ijms19082386
M3 - Article
C2 - 30104547
AN - SCOPUS:85052074007
VL - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 8
M1 - 2386
ER -