Antiplatelet and antithrombotic effects of cordycepin-enriched WIB-801CE from Cordyceps militaris ex vivo, in vivo, and in vitro

BMC Complementary and Alternative Medicine

Research Article

Ho-Kyun Kwon¹  Jun-Hee Noh¹  Je-Young Lee¹  Jong-Lae Kim¹  Hyuk-Woo Kwon²  Woo Jeong Ok²  Jung-Hae Shin²  Hwa-Jin Park²  Min Ji Kim²  Deok Hwi Lim²  Gi Suk Nam²  Hyun-Hong Kim² 

[1] Central Research Center, Whanin Pharm. Co., Ltd., 107, Gwanggyo-ro, 16229, Suwon, Gyeonggi-do, Korea;Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, 197, Inje-ro, Gyungnam, 50834, Gimhae, Korea;

关键词: WIB-801CE;    Cordycepin;    Platelet aggregation;    TXA;    Serotonin;    Thromboxane A synthase;    Arachidonic acid release;    p;    ERK2;    Thrombus;   

DOI  :  10.1186/s12906-016-1463-8

 received in 2016-06-01, accepted in 2016-11-16,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundA species of the fungal genus Cordyceps has been used as a complementary and alternative medicine of traditional Chinese medicine, and its major component cordycepin and cordycepin-enriched WIB-801CE are known to have antiplatelet effects in vitro. However, it is unknown whether they have also endogenous antiplatelet and antithrombotic effects. In this study, to resolve these doubts, we prepared cordycepin-enriched WIB-801CE, an ethanol extract from Cordyceps militaris-hypha, then evaluated its ex vivo, in vivo, and in vitro antiplatelet and antithrombotic effects.MethodsEx vivo effects of WIB-801CE on collagen- and ADP-induced platelet aggregation, serotonin release, thromboxane A2 (TXA2) production and its associated activities of enzymes [cyclooxygenase-1 (COX-1), TXA2 synthase (TXAS)], arachidonic acid (AA) release and its associated phosphorylation of phospholipase Cβ3, phospholipase Cγ2 or cytosolic phospholipase A2, mitogen-activated protein kinase (MAPK) [p38 MAPK, extracellular signal-regulated kinase (ERK)], and blood coagulation time in rats were investigated. In vivo effects of WIB-801CE on collagen plus epinephrine-induced acute pulmonary thromboembolism, and tail bleeding time in mice were also inquired. In vitro effects of WIB-801CE on cytotoxicity, and fibrin clot retraction in human platelets, and nitric oxide (NO) production in RAW264.7 cells or free radical scavenging activity were studied.ResultsCordycepin-enriched WIB-801CE inhibited ex vivo platelet aggregation, TXA2 production, AA release, TXAS activity, serotonin release, and p38 MAPK and ERK2 phosphorylation in collagen- and ADP-activated rat platelets without affecting blood coagulation. Furthermore, WIB-801CE manifested in vivo inhibitory effect on collagen plus epinephrine-induced pulmonary thromboembolism mice model. WIB-801CE inhibited in vitro NO production and fibrin clot retraction, but elevated free radical scavenging activity without affecting cytotoxicity against human platelets.ConclusionWIB-801CE inhibited collagen- and ADP-induced platelet activation and its associated thrombus formation ex vivo and in vivo. These were resulted from down-regulation of TXA2 production and its related AA release and TXAS activity, and p38MAPK and ERK2 activation. These results suggest that WIB-801CE has therapeutic potential to treat platelet activation-mediated thrombotic diseases in vivo.

【 授权许可】

CC BY   
© The Author(s). 2016