Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 865, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2019.172734
Keywords
Morin hydrate; Platelet aggregation; Integrin alpha(IIb)beta(3); Clot retraction; Cardiovascular disease; Thrombosis
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Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Korean Ministry of Education [2018R1D1A1B07047758]
- National Research Foundation of Korea [2018R1D1A1B07047758] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Morin hydrate is an active constituent of Morus alba L, Prunus dulcis, and Cudrania tricuspidata and has been reported to inhibit platelet activation in vivo and in vitro, but no reports have been issued on its regulation of alpha(IIb)beta(3), a platelet-specific integrin and thromboxane A(2) (TXA(2)), positive feedback molecule. In this study, we investigated the anti-platelet activity of morin hydrate in collagen- and thrombin-induced human platelets and attempted to identify the mechanism responsible for integrin alpha(IIb)beta(3) activation and TXA(2) generation. Our results demonstrated that morin hydrate (25-100 mu M) inhibited collagen- and thrombin-induced platelet aggregation, granule secretion (P-selectin expression, ATP, and serotonin release), calcium mobilization, TXA(2) production, integrin alpha(IIb)beta(3) activation, and clot retraction. Additionally, morin hydrate attenuated the phosphorylations of phospholipase C gamma(2) (PLC gamma(2)), cytosolic phospholipase A(2) (cPLA(2)), phosphoinositide 3-kinase (PI3K), Akt, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK), and enhanced the phosphorylations of inositol trisphosphate receptor (IP3 receptor) and cyclic adenosine monophosphate (cAMP) generation. However, it had no effect on the coagulation pathway. Taken together, these observations indicate morin hydrate inhibits platelet-mediated thrombosis by down-regulating TXA(2) production and integrin alpha(IIb)beta(3) activation, and by upregulating cAMP generation, and thus, inhibits clot retraction. These results suggest morin hydrate may have therapeutic potential as a treatment for platelet-activation-related diseases.
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