The Inhibitory Effects of Cordycepin on Phosphoproteins including PI3K, Akt, and p38

A species of Cordyceps, an ingredient in Chinese traditional medicine well-known for its major component, cordycepin (3'-deoxyadenosine), has been known to have antiplatelet effects; however, its effects on regulation of phosphoprotein have not been fully elucidated. In this study, we investigated how cordycepin regulates the phosphoprotein, including phosphatidylinositol 3-kinase (PI3K)/Akt and p38, to inhibit platelet aggregation, which are concerned with fibrinogen binding to glycoprotein IIb/IIIa (IIb/3) and granule secretion in platelets. Our finding suggests that cordycepin inhibits collagen-induced platelet aggregation with 261.1 M of IC50 and also inhibits fibrinogen binding to IIb/3 by a suppression of PI3K/Akt phosphorylation in a dose dependent manner. In addition, cordycepin further showed to inhibit collagen-induced p38 phosphorylation, reducing granule secretion (i.e. ATPand serotonin-release) and thromboxane A2 (TXA2) production without regulating cyclooxygenase-1 (COX-1) and thromboxane A synthase (TXAS) activities, as well as phospholipase C-2 (PLC-2) phosphorylation. In conclusion, these results demonstrate that cordycepin-mediated antiplatelet effects were due to the inhibition of fibrinogen binding to IIb/3 via the suppression of PI3K/Akt phosphorylation and inhibition of granule secretion & TXA2 production by suppressing p38 phosphorylation. These results strongly indicate that cordycepin might have therapeutic or preventive potential for platelet aggregation-mediated disorders, regulating the phosphoprotein, including PI3K/Akt and p38.