Antiplatelet effect of cudraxanthone B is related to inhibition of calcium mobilization, αIIbβ3 activation, and clot retraction

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.