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
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Lee, Dong-Ha
(Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University)
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Kim, Hyun-Hong
(Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University)
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Cho, Hyun-Jeong
(Department of Biomedical Laboratory Science, College of Medical Science, Konyang University)
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Yu, Young-Bin
(Department of Biomedical Laboratory Science, College of Medical Science, Konyang University)
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Kang, Hyo-Chan
(Department of Medical Laboratory Science, Dong-Eui Institute of Technology)
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Kim, Jong-Lae
(Bioscience & Biotechnology Team, Central Research Center, Whanin Pharm. Co., Ltd.)
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Lee, Jong-Jin
(Bioscience & Biotechnology Team, Central Research Center, Whanin Pharm. Co., Ltd.)
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Park, Hwa-Jin
(Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University)
published in 2014. 5. 31
Abstracts
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.
Keyword
- CE-WIB801C
- cAMP
- $TXA_2$
- $Ca^{2+}$
- $IP_3R$
Chemical Compound
(All 20)
(2R,3R,4S,5R)-2-(6-amino-9-purinyl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol | (2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol | (2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol | (2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-methylol-tetrahydrofuran-3,4-diol | adenosine
(C10H13N5O4)
Analytical Information
Analytical Information of the Articles
IPC |
A61K 31/7076, A61K 36/068, A61P 7/02, A61P 9/10 |
Analytical Keyword |
Cordyceps militaris; thrombosis; myocardial infarction; atherosclerosis; ischemic cerebrovascular disease; platelet aggregation-mediated diseases; cordycepin-enriched WIB801C; cAMP-dependent phosphorylation; inositol 1, 4, 5-trisphosphate receptor; collagen; Ca2+ mobilization=calcium ion mobilization; thromboxane A2=TXA2
|
Herb keywrd |
Cordyceps militaris
|
Disease keywrd |
thrombosis; myocardial infarction; atherosclerosis; ischemic cerebrovascular disease; platelet aggregation-mediated diseases
|
Etc. keywrd |
cordycepin-enriched WIB801C; cAMP-dependent phosphorylation; inositol 1, 4, 5-trisphosphate receptor; collagen; Ca2+ mobilization=calcium ion mobilization; thromboxane A2=TXA2
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Published Information of the Articles
Country |
kor |
Publisher |
The Korean Society of Applied Pharmacology |
KJTK Publish Information |
Volume 8.
2014. 12. 31
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