Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, 197, Inje-ro, Gimhae, Gyungnam, 621-749, Republic of Korea.
Arch Pharm Res. 2015 Jan;38(1):81-97. doi: 10.1007/s12272-014-0436-z. Epub 2014 Jul 9.
In this study, we investigated the effect of cordycepin-enriched (CE)-WIB801C from Cordyceps militaris on ADP (20 µM)-stimulated platelet aggregation. CE-WIB801C dose-dependently inhibited ADP-induced platelet aggregation, and its IC50 value was 18.5 μg/mL. CE-WIB801C decreased TXA2 production, but did not inhibit the activities of COX-1 and thromboxane synthase (TXAS) in ADP-activated platelets, which suggests that the inhibition of TXA2 production by CE-WIB801C is not resulted from the direct inhibition of COX-1 and TXAS. CE-WIB801C inhibited ATP release and [Ca(2+)]i mobilization, and increased cAMP level and IP3RI (Ser(1756)) phosphorylation in ADP-activated platelets. cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased CE-WIB801C-inhibited [Ca(2+)]i mobilization, and strongly inhibited CE-WIB801C-increased IP3RI (Ser(1756)) phosphorylation. CE-WIB801C elevated the phosphorylation of VASP (Ser(157)), an A-kinase substrate, but inhibited fibrinogen binding to αIIb/β3. These results suggest that CE-WIB801C-elevated cAMP involved in IP3RI (Ser(1756)) phosphorylation to inhibit [Ca(2+)]i mobilization and, VASP (Ser(157)) phosphorylation to inhibit αIIb/β3 activation. Therefore, in this study, we demonstrate that CE-WIB801C may have a preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.
在这项研究中，我们研究了蛹虫草来源的虫草素富集物（CE）-WIB801C 对 ADP（20 μM）诱导的血小板聚集的影响。CE-WIB801C 呈剂量依赖性抑制 ADP 诱导的血小板聚集，其 IC50 值为 18.5 μg/mL。CE-WIB801C 降低 TXA2 的产生，但不抑制 ADP 激活的血小板中环氧化酶-1（COX-1）和血栓烷合酶（TXAS）的活性，这表明 CE-WIB801C 抑制 TXA2 的产生不是由于直接抑制 COX-1 和 TXAS。CE-WIB801C 抑制 ADP 激活的血小板中 ATP 释放和 [Ca(2+)]i 动员，并增加 cAMP 水平和 IP3RI（Ser(1756)）磷酸化。cAMP 依赖性蛋白激酶（A-激酶）抑制剂 Rp-8-Br-cAMPS 增加了 CE-WIB801C 抑制的 [Ca(2+)]i 动员，并强烈抑制了 CE-WIB801C 增加的 IP3RI（Ser(1756)）磷酸化。CE-WIB801C 升高了 A-激酶底物 VASP（Ser(157)）的磷酸化，但抑制了纤维蛋白原与 αIIb/β3 的结合。这些结果表明，CE-WIB801C 升高的 cAMP 参与 IP3RI（Ser(1756)）磷酸化以抑制 [Ca(2+)]i 动员，以及 VASP（Ser(157)）磷酸化以抑制 αIIb/β3 的激活。因此，在这项研究中，我们证明 CE-WIB801C 可能具有预防或治疗血小板聚集介导的疾病的潜力，例如血栓形成、心肌梗死、动脉粥样硬化和缺血性脑血管病。
