Inhibitory effect of caffeic acid on ADP-induced thrombus formation and platelet activation involves mitogen-activated protein kinases

Caffeic acid (CA), one of the active constituents of Radix Salvia miltiorrhizae, exhibits antioxidant and anti-inflammatory activities. However, few studies have assessed the ability of CA to inhibit platelet mediated thrombus generation in vivo. In this study, we investigated the antithrombotic effect of CA in mouse cerebral arterioles and venules using intravital microscopy. The antiplatelet activity of CA in ADP stimulated mouse platelets in vitro was also examined in attempt to explore the underlying mechanism. Our results demonstrated that CA (1.25-5 mg/kg) significantly inhibited thrombus formation in vivo. In vitro, CA (25-100 mu M) inhibited ADP-induced platelet aggregation, P-selectin expression, ATP release, Ca2+ mobilization, and integrin alpha IIb beta 3 activation. Additionally, CA attenuated p38, ERK, and JNK activation, and enhanced cAMP levels. Taken together, these data provide evidence for the inhibition of CA on platelet-mediated thrombosis in vivo, which is, at least partly, mediated by interference in phosphorylation of ERK, p38, and JNK leading to elevation of cAMP and down-regulation of P-selectin expression and alpha IIb beta 3 activation. These results suggest that CA may have potential for the treatment of aberrant platelet activation-related diseases.Production of New Medicine Program of Ministry of Science and Technology of the People's Republic of China [2013ZX09402202]SCI(E)PubMedARTICLEchuanshe@bjmu.edu.cn; hanjingyan@bjmu.edu.cn13824