TY - JOUR
T1 - Licochalcone a prevents platelet activation and thrombus formation through the inhibition of PLCγ2-PKC, Akt, and MAPK pathways
AU - Lien, Li Ming
AU - Lin, Kuan Hung
AU - Huang, Li Ting
AU - Tseng, Mei Fang
AU - Chiu, Hou Chang
AU - Chen, Ray Jade
AU - Lu, Wan Jung
N1 - Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2017/7/12
Y1 - 2017/7/12
N2 - Platelet activation is involved in cardiovascular diseases, such as atherosclerosis and ischemic stroke. Licochalcone A (LA), an active ingredient of licorice, exhibits multiple biological activities such as anti-oxidation and anti-inflammation. However, its role in platelet activation remains unclear. Therefore, the study investigated the antiplatelet mechanism of LA. Our data revealed that LA (2–10 µM) concentration dependently inhibited platelet aggregation induced by collagen, but not thrombin and U46619. LA markedly attenuated collagen-stimulated ATP release, P-selectin secretion, calcium mobilization, and GPIIbIIIa activation, but did not interfere with the collagen binding to platelets. Moreover, LA significantly reduced the activation of PLCγ2, PKC, Akt and MAPKs. Thus, LA attenuates platelet activation, possibly by inhibiting collagen receptor downstream signaling but not by blocking the collagen receptors. In addition, LA prevented adenosine diphosphate (ADP)-induced acute pulmonary thrombosis, fluorescein sodium-induced platelet thrombus formation, and middle cerebral artery occlusion/reperfusion-induced brain injury in mice, but did not affect normal hemostasis. This study demonstrated that LA effectively reduced platelet activation and thrombus formation, in part, through the inhibition of PLCγ2–PKC, Akt, and MAPK pathways, without the side effect of bleeding. These findings also indicate that LA may provide a safe and alternative therapeutic approach for preventing thromboembolic disorders such as stroke.
AB - Platelet activation is involved in cardiovascular diseases, such as atherosclerosis and ischemic stroke. Licochalcone A (LA), an active ingredient of licorice, exhibits multiple biological activities such as anti-oxidation and anti-inflammation. However, its role in platelet activation remains unclear. Therefore, the study investigated the antiplatelet mechanism of LA. Our data revealed that LA (2–10 µM) concentration dependently inhibited platelet aggregation induced by collagen, but not thrombin and U46619. LA markedly attenuated collagen-stimulated ATP release, P-selectin secretion, calcium mobilization, and GPIIbIIIa activation, but did not interfere with the collagen binding to platelets. Moreover, LA significantly reduced the activation of PLCγ2, PKC, Akt and MAPKs. Thus, LA attenuates platelet activation, possibly by inhibiting collagen receptor downstream signaling but not by blocking the collagen receptors. In addition, LA prevented adenosine diphosphate (ADP)-induced acute pulmonary thrombosis, fluorescein sodium-induced platelet thrombus formation, and middle cerebral artery occlusion/reperfusion-induced brain injury in mice, but did not affect normal hemostasis. This study demonstrated that LA effectively reduced platelet activation and thrombus formation, in part, through the inhibition of PLCγ2–PKC, Akt, and MAPK pathways, without the side effect of bleeding. These findings also indicate that LA may provide a safe and alternative therapeutic approach for preventing thromboembolic disorders such as stroke.
KW - Licochalcone A
KW - Middle cerebral artery occlusion
KW - Platelet activation
KW - PLCγ2-PKC
KW - Thrombus formation
UR - http://www.scopus.com/inward/record.url?scp=85024132888&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85024132888&partnerID=8YFLogxK
U2 - 10.3390/ijms18071500
DO - 10.3390/ijms18071500
M3 - Article
C2 - 28704925
AN - SCOPUS:85024132888
SN - 1661-6596
VL - 18
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 7
M1 - 1500
ER -