Biomol Ther.  2014 May;22(3):223-231.

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

Affiliations
  • 1Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, Gimhae 621-749, Republic of Korea. mlsjpark@inje.ac.kr
  • 2Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon 302-718, Republic of Korea.
  • 3Department of Medical Laboratory Science, Dong-Eui Institute of Technology, Busan 614-715, Republic of Korea.
  • 4Bioscience & Biotechnology Team, Central Research Center, Whanin Pharm. Co., Ltd., Suwon 443-766, Republic of Korea.

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 IC50 value was 175 microg/ml. CE-WIB801C increased cAMP level more than cGMP level, but inhibited collagen-elevated [Ca2+]i mobilization and thromboxane A2 (TXA2) production. cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased the CE-WIB801C-downregulated [Ca2+]i level in a dose dependent manner, and strongly inhibited CE-WIB801C-induced inositol 1, 4, 5-trisphosphate receptor (IP3R) phosphorylation. These results suggest that the inhibition of [Ca2+]i mobilization by CE-WIB801C is resulted from the cAMP/A-kinase-dependent phosphorylation of IP3R. CE-WIB801C suppressed TXA2 production, but did not inhibit the activities of cyclooxygenase-1 (COX-1) and TXA2 synthase (TXAS). These results suggest that the inhibition of TXA2 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 Ca2+-antagonistic antiplatelet effects may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

Keyword

CE-WIB801C; cAMP; TXA2; Ca2+; IP3R

MeSH Terms

1-Butanol
Atherosclerosis
Blood Platelets
Cordyceps*
Cyclic AMP-Dependent Protein Kinases
Cyclooxygenase 1
Humans
Inhibitory Concentration 50
Inositol*
Myocardial Infarction
Phosphorylation*
Platelet Aggregation
Thrombosis
Thromboxane A2
1-Butanol
Cyclic AMP-Dependent Protein Kinases
Cyclooxygenase 1
Inositol
Thromboxane A2
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