Pharmacological actions of morusinol on modulation of platelet functions via integrin αIIb/β3 signaling

Morus alba, a popular medicinal plant belonging to the family Moraceae, has long been used commonly in traditional medicine and has various physiological activities, including antidiabetic, anti-microbial, diuretic, anti-oxidant, and anti-cancer activities. Morusinol was isolated from the root bark of M. alba; however, its biological effects have not yet been reported. Therefore, we examined the inhibitory effects of morusinol on human platelet aggregation, Ca 2+ mobilization, and IIb/ 3 activity. Our data showed that collagen-induced human platelet aggregation was inhibited by morusinol without cytotoxicity. In this study, we examined whether morusinol inhibits platelet aggregation through the regulation of integrin IIb/ 3 and its associated signaling molecules. We observed that morusinol inhibited IIb/ 3 activation by regulating vasodilator-stimulated phosphoprotein, phosphatidylinositol-3 kinase, Akt (protein kinase B), and glycogen synthase kinase-3/. These results show that morusinol inhibited fibronectin adhesion, fibrinogen binding, and clot retraction. Taken together, morusinol shows strong antiplatelet and anti-clot retraction effects and is a potential therapeutic drug candidate to prevent plateletrelated thrombosis and cardiovascular disease.