Cordycepin-enriched WIB801C from Cordyceps militaris inhibits ADP-induced [Ca(2+)] i mobilization and fibrinogen binding via phosphorylation of IP 3R and VASP.

Abstract

In this study, we investigated the effect of cordycepin-enriched (CE)-WIB801C from Cordyceps militaris on ADP (20 µM)-stimulated platelet aggregation. CE-WIB801C dose-dependently inhibited ADP-induced platelet aggregation, and its IC50 value was 18.5 μg/mL. CE-WIB801C decreased TXA2 production, but did not inhibit the activities of COX-1 and thromboxane synthase (TXAS) in ADP-activated platelets, which suggests that the inhibition of TXA2 production by CE-WIB801C is not resulted from the direct inhibition of COX-1 and TXAS. CE-WIB801C inhibited ATP release and [Ca(2+)]i mobilization, and increased cAMP level and IP3RI (Ser(1756)) phosphorylation in ADP-activated platelets. cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased CE-WIB801C-inhibited [Ca(2+)]i mobilization, and strongly inhibited CE-WIB801C-increased IP3RI (Ser(1756)) phosphorylation. CE-WIB801C elevated the phosphorylation of VASP (Ser(157)), an A-kinase substrate, but inhibited fibrinogen binding to αIIb/β3. These results suggest that CE-WIB801C-elevated cAMP involved in IP3RI (Ser(1756)) phosphorylation to inhibit [Ca(2+)]i mobilization and, VASP (Ser(157)) phosphorylation to inhibit αIIb/β3 activation. Therefore, in this study, we demonstrate that CE-WIB801C may have a preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

• Authors: Dong-Ha Lee, Hyuk-Woo Kwon, Hyun-Hong Kim, Deok Hwi Lim, Gi Suk Nam, Jung-Hae Shin, Yun-Yi Kim, Jong-Lae Kim, Jong-Jin Lee, Ho-Kyun Kwon, Hwa-Jin Park
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 38 Issue 1 Pg. 81-97 (Jan 2015) ISSN: 1976-3786 [Electronic] Korea (South)
• PMID: 25001901 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 8-bromoadenosine-3',5'-cyclic monophosphorothioate
• Cell Adhesion Molecules
• Deoxyadenosines
• Inositol 1,4,5-Trisphosphate Receptors
• Microfilament Proteins
• Phosphoproteins
• Plant Extracts
• Platelet Aggregation Inhibitors
• Thionucleotides
• WIB801C
• vasodilator-stimulated phosphoprotein
• 8-Bromo Cyclic Adenosine Monophosphate
• Thromboxane A2
• Adenosine Diphosphate
• Adenosine Triphosphate
• Fibrinogen
• Cyclic AMP
• Cyclooxygenase 1
• Thromboxane-A Synthase
• cordycepin
• Calcium

Topics

• 8-Bromo Cyclic Adenosine Monophosphate (analogs & derivatives, pharmacology)
• Adenosine Diphosphate (pharmacology)
• Adenosine Triphosphate (metabolism)
• Blood Platelets (drug effects, metabolism)
• Calcium (metabolism)
• Calcium Signaling (drug effects)
• Cell Adhesion Molecules (metabolism)
• Cordyceps (chemistry)
• Cyclic AMP (metabolism)
• Cyclooxygenase 1 (metabolism)
• Deoxyadenosines (pharmacology)
• Dose-Response Relationship, Drug
• Fibrinogen (metabolism)
• Herb-Drug Interactions
• Humans
• Inositol 1,4,5-Trisphosphate Receptors (metabolism)
• Microfilament Proteins (metabolism)
• Phosphoproteins (metabolism)
• Phosphorylation (drug effects)
• Plant Extracts (chemistry, pharmacology)
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (pharmacology)
• Thionucleotides (pharmacology)
• Thromboxane A2 (metabolism)
• Thromboxane-A Synthase (metabolism)