Chrysophanol-8-O-glucoside Attenuates Platelet Activation Through Inhibiting MAPK and PKCε

Platelets are key components of thrombosis and may also participate in the progression of cardiovascular diseases. Hence, the inhibition of platelet aggregation is important for preventing the progression of arterial thrombosis. Rhubarb is a widely used traditional medicine and has been reported to elicit a number of biological effects including antiinflammatory and antiplatelet effects. In the present study, we investigated the effect and mechanism of anthraquinone derivative isolated from rhubarb on platelet activity. Of four anthraquinone derivatives isolated from rhubarb examined, chrysophanol-8-O-glucoside (CP-8-O-glc) was found to have the most potent inhibitory effect on collagen- and thrombininduced platelet aggregation. CP-8-O-glc-treated mice showed significantly prolonged bleeding times. Furthermore, CP-8-O-glc-glucoside was found to have a significant inhibitory effect on rat platelet aggregation ex vivo. In coagulation tests, CP-8-O-glcglucoside did not alter prothrombin time (PT), and it prolonged the activated partial thromboplastin time (aPTT). However, CP-8-O-glc only inhibited platelet phosphatidylserine exposure, but not direct inhibition on intrinsic factors. To reveal the inhibition mechanism of CP-8-O-glc on platelet activation, we examined the effects of CP-8-O-glc on MAPKs, Akt, PKCε activation. ERK2, JNK1, Akt, and PKCε were significantly activated during collagen-induced aggregation, and the observation was inhibited by ERK inhibitor and CP-8-O-glc, which subsequently contributes to antiplatelet mechanism of CP-8-O-glc. On the other hand, the activation of p38 during collagen-induced aggregation was not inhibited by CP-8-O-glc. Taken together, these results suggest that the ERK2 is a major actor in collagen-induced platelet functional responses, acting as upstream of Akt, JNK1, and PKCε and that antiplatelet activity of CP-8-O-glc may involve an inhibition of ERK2 activation. This study demonstrates the antiplatelet and anticoagulant effects of CP-8-O-glc and its pivotal mechanisms, and suggests that this compound might be of therapeutic benefit for the prevention of platelet-related cardiovascular diseases.

Author dc:creator

• 서, 은지

Contributors dc:contributor

• 이, 수환
• 정, 이숙
• 대학원 의생명과학과
• 104644

• Chrysophanol-8-O-glucoside
• antiplatelet
• anthraquinone derivative
• anticoagulant

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000012955
000000012955

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/7530