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 μM) inhibited ADP-induced platelet aggregation, P-selectin expression, ATP release, Ca(2+) mobilization, and integrin αIIbβ3 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 αIIbβ3 activation. These results suggest that CA may have potential for the treatment of aberrant platelet activation-related diseases.
Department of gynaecology, Beijing Royal Integrative Medicine Hospital, Beijing, China.|Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China.|Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
Yu
Y
Lu
Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.|Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China.
Quan
Q
Li
Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.|Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China.
Yu-Ying
YY
Liu
Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.|Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China.
Kai
K
Sun
Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
Jing-Yu
JY
Fan
Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China.|Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.|Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China.
Chuan-She
CS
Wang
Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China.|Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.|Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China.
Jing-Yan
JY
Han
D000244:Adenosine Diphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology*; D055252:Cell-Derived Microparticles / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D013927:Thrombosis / Q000188:drug therapy / Q000209:etiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002109:Caffeic Acids; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C040048:caffeic acid