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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

Effect of CA on production of platelet-derived microparticles (PMPs).(A) PMPs were detected by flow cytometry with the fluorescence gate designed for Annexin V-FITC and CD41-PE double-positive events. (B) Quantitative evaluation of PMPS in different conditions. Data are expressed as means ± SEM (n = 6). *p < 0.05 vs control group, #p < 0.05 vs ADP group.
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f6: Effect of CA on production of platelet-derived microparticles (PMPs).(A) PMPs were detected by flow cytometry with the fluorescence gate designed for Annexin V-FITC and CD41-PE double-positive events. (B) Quantitative evaluation of PMPS in different conditions. Data are expressed as means ± SEM (n = 6). *p < 0.05 vs control group, #p < 0.05 vs ADP group.

Mentions: In view of the important role of microparticles in regulation of platelet-rich thrombosis, we assessed whether CA could inhibit PMPs production by flow cytometry. The result is presented in Fig. 6, wherein PMPs production is expressed as percentage of Annexin V+/CD41+. Obviously, ADP stimulation caused a significant increase in PMPs production, which was protected from by pretreatment with CA at 100 μM.


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)

Effect of CA on production of platelet-derived microparticles (PMPs).(A) PMPs were detected by flow cytometry with the fluorescence gate designed for Annexin V-FITC and CD41-PE double-positive events. (B) Quantitative evaluation of PMPS in different conditions. Data are expressed as means ± SEM (n = 6). *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

f6: Effect of CA on production of platelet-derived microparticles (PMPs).(A) PMPs were detected by flow cytometry with the fluorescence gate designed for Annexin V-FITC and CD41-PE double-positive events. (B) Quantitative evaluation of PMPS in different conditions. Data are expressed as means ± SEM (n = 6). *p < 0.05 vs control group, #p < 0.05 vs ADP group.
Mentions: In view of the important role of microparticles in regulation of platelet-rich thrombosis, we assessed whether CA could inhibit PMPs production by flow cytometry. The result is presented in Fig. 6, wherein PMPs production is expressed as percentage of Annexin V+/CD41+. Obviously, ADP stimulation caused a significant increase in PMPs production, which was protected from by pretreatment with CA at 100 μM.

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