Abstract
Cudrania tricuspidata (C. tricuspidata) is widespread throughout Asia and has known to have various physiological activities such as, inflammation, diabetes, obesity and tumor. Cudrania tricuspidata, a rich source of xanthones and flavonoids, have been investigated phytochemically and biologically. However, research of these compounds on platelets is limited. Therefore, we searched for a new substance from various xanthones and flavonoids in C. tricuspidata. We confirmed the results that steppogenin and isoderrone suppress human platelets among the various components isolated from C. tricuspidata, and as a result of analyzing the antiplatelet effect using additional new samples, we found that cudraxanthone B (CXB) has the effect of suppressing human platelets. Therefore, we studied the potential efficacies of CXB on human platelet aggregation and its inhibitory mechanism. Inhibitory effects of CXB on platelet aggregation were assessed using washed platelets, followed by measurement of [Ca2+]i mobilization and dense granule release, fibrinogen binding, fibronectin adhesion assay, and clot retraction. Our data showed that CXB suppressed collagen-induced human platelet aggregation, [Ca2+]i mobilization, fibrinogen binding, fibronectin adhesion and clot retraction without cytotoxicity. Thus, our results show that inhibitory effects of CXB on human platelet activation and thrombus formation, suggesting its potential use as a natural substance for preventing platelet-induced thrombosis.
Highlights
An area of damaged vascular wall exposures collagen and circulatory platelets can bind to the collagen through receptors of α2β1 and glycoprotein VI on platelet surface
Inhibitory effects of cudraxanthone B (CXB) on fibrinogen binding to integrin αIIb/β3 and fibronectin adhesion we investigated fibrinogen binding to αIIb/β3, which is an important reaction in outside-in signaling
As CXB showed the inhibitory action on collageninduced αIIb/β3 activation (Fig. 3A, C), we investigated the effect of CXB on Vasodilator-stimulated phosphoprotein (VASP) Ser157 phosphorylation in collagen-stimulated platelets
Summary
An area of damaged vascular wall exposures collagen and circulatory platelets can bind to the collagen through receptors of α2β1 and glycoprotein VI on platelet surface. IP3 mediated calcium mobilization activates calcium/ calmodulin-dependent Myosin light-chain (MLC) kinase and phosphorylates MLC affecting granule release. These signaling cascades are called “inside-out signaling” and facilitates interaction with plasma adhesive molecules (i.e. fibrinogen, fibronectin, vitronectin) and glycoprotein IIb/IIIa ( called αIIb/β3). After interaction between adhesive molecules with αIIbβ3, “outside-in signaling” is subsequently processed to promote platelet aggregation affecting thrombus formation [3]. The production of thrombosis is a fatal risk for patients who have thrombus mediated cardiovascular disease. More various anti-platelet drugs and functional food are necessary without serious complications [4, 5]. Further research is needed for the development of more effective and safer drugs to ensure better treatment and prevention of cardiovascular disease
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