Artocarpesin Prevents Collagen Induced Platelet Aggregation and Clot Retraction Through Cyclic Nucleotides and Dephosphorylation of MAPKs

Background The cardiovascular diseases (CVDs) are becoming a critical threat to our lives in these years. It is now widely accepted that platelets play an important role in cardiovascular disease as they have a fundamental role in thrombosis. Therefore, many drugs or natural substances have been developed to treat CVDs. Cudrania tricuspidata ( C. tricuspidata ) is a regional plant containing various flavonoids and xanthones, and various physiological activities have been reported. Therefore, we evaluated antiplatelet effects using artocarpesin isolated from C. tricuspidata. Methods The in vitro effects of artocarpesin on platelets was assessed using measurement of calcium mobilization and serotonin release, glycoprotein IIb/IIIa activation, clot retraction and phosphorylation of signaling molecules. Results Artocarpesin inhibited human platelet aggregation, calcium mobilization, glycoprotein IIb/IIIa activation and thrombin-induced clot retraction through the regulation of associated signaling molecules such as vasodilator-stimulated phosphoprotein (VASP) and inositol 1, 4, 5-triphosphate receptor I (IP 3 RI), and on the dephosphorylation of cytosolic phospholipase A 2 (cPLA 2 ), mitogen-activated protein kinases p38, JNK and phosphoinositide 3-kinase (PI3K)/Akt. Conclusions This study highlights that artocarpesin has inhibitory effects on platelet activities and thrombus formation and has potential value for preventing platelet-induced cardiovascular diseases.