Atherothrombosis is one of the main underlying cause of
cardiovascular diseases. In addition to treating
atherothrombosis with
antithrombotic agents, there is growing interest in the role of natural food products and biologically active ingredients for the prevention and treatment of
cardiovascular diseases. This study aimed to investigate the effect of
secolincomolide A (3) isolated from Lindera obtusiloba Blume on platelet activity and identify possible signaling pathways. In our study, the antiplatelet activities of 3 were measured by
collagen-induced platelet aggregation and
serotonin secretion in freshly isolated rabbit platelets. Interestingly, 3 effectively inhibited the
collagen-induced platelet aggregation and
serotonin secretion via decreased production of
diacylglycerol,
arachidonic acid, and
cyclooxygenase-mediated metabolites such as
thromboxane B2 (TXB2), and
prostaglandin D2 (
PGD2). In accordance with the antiplatelet activities, 3 prolonged bleeding time and attenuated FeCl3-induced
thrombus formation in arterial
thrombosis model. Notably, 3 abolished the phosphorylation of
phospholipase Cγ2 (PLCγ2),
spleen tyrosine kinase (Syk), p47,
extracellular signal-regulated kinase 1/2 (ERK1/2),
protein kinase B (Akt) by inhibiting the activation of the
collagen receptor,
glycoprotein VI (GPVI). Taken together, our results indicate the therapeutic potential of 3 in antiplatelet action through inhibition of the GPVI-mediated signaling pathway and the COX-1-mediated AA metabolic pathways.