title: Cordycepin-Enriched WIB801C from Cordyceps militaris Inhibits Collagen-Induced [Ca(2+)]i Mobilization via cAMP-Dependent Phosphorylation of Inositol 1, 4, 5-Trisphosphate Receptor in Human Platelets.
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 μg/ml. CE-WIB801C increased cAMP level more than cGMP level, but inhibited collagen-elevated [Ca(2+)]i mobilization and thromboxane A2 (TXA2) 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 (IP3R) 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 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 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.
authors.affiliation: Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, Gimhae 621-749.
authors.forename: Dong-Ha
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, Gimhae 621-749.
authors.forename: Hyun-Hong
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon 302-718.
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon 302-718.
authors.forename: Young-Bin
authors.initials: YB
authors.lastname: Yu
authors.affiliation: Department of Medical Laboratory Science, Dong-Eui Institute of Technology, Busan 614-715.
authors.forename: Hyo-Chan
authors.initials: HC
authors.lastname: Kang
authors.affiliation: Bioscience & Biotechnology Team, Central Research Center, Whanin Pharm. Co., Ltd., Suwon 443-766, Republic of Korea.
authors.forename: Jong-Lae
authors.initials: JL
authors.lastname: Kim
authors.affiliation: Bioscience & Biotechnology Team, Central Research Center, Whanin Pharm. Co., Ltd., Suwon 443-766, Republic of Korea.
authors.forename: Jong-Jin
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, Gimhae 621-749.
authors.forename: Hwa-Jin
authors.initials: HJ
authors.lastname: Park
keywords: CE-WIB801C; Ca2+; IP3R; TXA2; cAMP