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Cordycepin-Enriched WIB801C from Cordyceps militaris Inhibits Collagen-Induced [Ca2+]i Mobilization via cAMP-Dependent Phosphorylation of Inositol 1, 4, 5-Trisphosphate Receptor in Human Platelets

  • Lee, Dong-Ha (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University) ;
  • Kim, Hyun-Hong (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University) ;
  • Cho, Hyun-Jeong (Department of Biomedical Laboratory Science, College of Medical Science, Konyang University) ;
  • Yu, Young-Bin (Department of Biomedical Laboratory Science, College of Medical Science, Konyang University) ;
  • Kang, Hyo-Chan (Department of Medical Laboratory Science, Dong-Eui Institute of Technology) ;
  • Kim, Jong-Lae (Bioscience & Biotechnology Team, Central Research Center, Whanin Pharm. Co., Ltd.) ;
  • Lee, Jong-Jin (Bioscience & Biotechnology Team, Central Research Center, Whanin Pharm. Co., Ltd.) ;
  • Park, Hwa-Jin (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University)
  • Received : 2014.02.26
  • Accepted : 2014.05.12
  • Published : 2014.05.31

Abstract

In this study, we prepared cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha, and investigated the effect of CE-WIB801C on collagen-induced human platelet aggregation. CE-WIB801C dose-dependently inhibited collagen-induced platelet aggregation, and its $IC_{50}$ value was $175{\mu}g/ml$. CE-WIB801C increased cAMP level more than cGMP level, but inhibited collagen-elevated $[CA^{2+}]_i$ mobilization and thromboxane $A_2$ ($TXA_2$) production. cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased the CE-WIB801C-downregulated $[CA^{2+}]_i$ level in a dose dependent manner, and strongly inhibited CE-WIB801C-induced inositol 1, 4, 5-trisphosphate receptor ($IP_3R$) phosphorylation. These results suggest that the inhibition of $[CA^{2+}]_i$ mobilization by CE-WIB801C is resulted from the cAMP/A-kinase-dependent phosphorylation of $IP_3R$. CE-WIB801C suppressed $TXA_2$ production, but did not inhibit the activities of cyclooxygenase-1 (COX-1) and $TXA_2$ synthase (TXAS). These results suggest that the inhibition of $TXA_2$ production by WIB801C is not resulted from the direct inhibition of COX-1 and TXAS. In this study, we demonstrate that CE-WIB801C with cAMP-dependent $CA^{2+}$-antagonistic antiplatelet effects may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

Keywords

References

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