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

Lu Y, Li Q, Liu YY, Sun K, Fan JY, Wang CS, Han JY - Sci Rep (2015)

Bottom Line: In this study, we investigated the antithrombotic effect of CA in mouse cerebral arterioles and venules using intravital microscopy.Our results demonstrated that CA (1.25-5 mg/kg) significantly inhibited thrombus formation in vivo.Additionally, CA attenuated p38, ERK, and JNK activation, and enhanced cAMP levels.

View Article: PubMed Central - PubMed

Affiliation: Department of gynaecology, Beijing Royal Integrative Medicine Hospital, Beijing, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

CA elevates cAMP levels in ADP stimulated platelets.Platelets were preincubated with or without CA in the presence of CaCl2 (1 mM) at 37 °C for 20 min and then stimulated with ADP for 20 min. cAMP level was determined with a Cyclic AMP XP® Chemiluminescent Assay Kit. CA significantly increased cAMP levels in ADP-stimulated platelets in a concentration-dependent manner. Data are expressed as means ± SEM (n = 10). *p < 0.05 vs control group, #p < 0.05 vs ADP group.
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f7: CA elevates cAMP levels in ADP stimulated platelets.Platelets were preincubated with or without CA in the presence of CaCl2 (1 mM) at 37 °C for 20 min and then stimulated with ADP for 20 min. cAMP level was determined with a Cyclic AMP XP® Chemiluminescent Assay Kit. CA significantly increased cAMP levels in ADP-stimulated platelets in a concentration-dependent manner. Data are expressed as means ± SEM (n = 10). *p < 0.05 vs control group, #p < 0.05 vs ADP group.

Mentions: Since cAMP generation and the resulted protein kinase activation are known to inhibit platelet activation, we next determined whether CA alters cAMP levels in ADP-activated platelets. As shown in Fig. 7, the cAMP level in the ADP stimulated platelets was significantly decreased compared with that in the quiescent platelets. Noticeably, CA (5–100 μM) significantly increased the cAMP level in the platelets exposed to ADP in a dose-dependent manner.


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

Lu Y, Li Q, Liu YY, Sun K, Fan JY, Wang CS, Han JY - Sci Rep (2015)

CA elevates cAMP levels in ADP stimulated platelets.Platelets were preincubated with or without CA in the presence of CaCl2 (1 mM) at 37 °C for 20 min and then stimulated with ADP for 20 min. cAMP level was determined with a Cyclic AMP XP® Chemiluminescent Assay Kit. CA significantly increased cAMP levels in ADP-stimulated platelets in a concentration-dependent manner. Data are expressed as means ± SEM (n = 10). *p < 0.05 vs control group, #p < 0.05 vs ADP group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561902&req=5

f7: CA elevates cAMP levels in ADP stimulated platelets.Platelets were preincubated with or without CA in the presence of CaCl2 (1 mM) at 37 °C for 20 min and then stimulated with ADP for 20 min. cAMP level was determined with a Cyclic AMP XP® Chemiluminescent Assay Kit. CA significantly increased cAMP levels in ADP-stimulated platelets in a concentration-dependent manner. Data are expressed as means ± SEM (n = 10). *p < 0.05 vs control group, #p < 0.05 vs ADP group.
Mentions: Since cAMP generation and the resulted protein kinase activation are known to inhibit platelet activation, we next determined whether CA alters cAMP levels in ADP-activated platelets. As shown in Fig. 7, the cAMP level in the ADP stimulated platelets was significantly decreased compared with that in the quiescent platelets. Noticeably, CA (5–100 μM) significantly increased the cAMP level in the platelets exposed to ADP in a dose-dependent manner.

Bottom Line: In this study, we investigated the antithrombotic effect of CA in mouse cerebral arterioles and venules using intravital microscopy.Our results demonstrated that CA (1.25-5 mg/kg) significantly inhibited thrombus formation in vivo.Additionally, CA attenuated p38, ERK, and JNK activation, and enhanced cAMP levels.

View Article: PubMed Central - PubMed

Affiliation: Department of gynaecology, Beijing Royal Integrative Medicine Hospital, Beijing, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus