Antithrombotic effect and antiplatelet activity of moracin M

Platelet-induced thrombosis and platelet hyper-activation processes are critical drivers of cardiovascular diseases (CVD). Platelets are central to the development and progression of many forms of CVD, playing a dual role in hemostasis and thrombosis. Under physiological conditions, they maintain vascular integrity by rapidly forming clots at sites of vascular injury. However, when excessively activated, platelets contribute to pathological thrombus formation and promote atherosclerotic processes, thereby increasing the risk of myocardial infarction and stroke. While various drugs have been developed to treat cardiovascular disease, we focused on prevention and explored various natural products. Among the various candidates, we discovered moracin M and analyzed the antiplatelet action. Human platelets were treated with moracin M to evaluate its effects on aggregation, intracellular signaling, granule secretion, and clot retraction. Moracin M inhibited platelet aggregation in a dosedependent manner following stimulation with collagen. It suppressed Ca2+ mobilization, dense granule secretion, and phosphorylation of key signaling molecules, including InsP₃R, ERK1/2, p38, JNK, cPLA2, Akt, Syk and VASP. Additionally, moracin M inhibited integrin αIIbβ3 activation, reduced platelet adhesion, and thrombininduced clot retraction.