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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

Chemical structure of caffeic acid (CA).
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f1: Chemical structure of caffeic acid (CA).

Mentions: Caffeic acid (CA) is one of the major water-soluble components of Radix Salvia miltiorrhiza. The chemical structure of CA is illustrated in Fig. 1. Accumulating evidence has confirmed that CA has potent antioxidant and anti-inflammatory activities1617. Previous studies showed that CA can inhibit the cyclooxygenase activity and the adhesion protein P-selectin expression in platelets in vitro181920. A recent study demonstrated the potential of CA to inhibit collagen-induced platelet aggregation via cAMP-dependent inositol-1,4,5-trisphosphate receptor phosphorylation21. However, little is known regarding the role of CA in platelet mediated thrombus generation in vivo, and the mechanism thereby the influence of CA on ADP-induced platelet activation has not been fully understood. The aim of this study was to examine the effects of CA on platelet mediated thrombosis in mouse cerebral microvessels and characterize the underlying mechanisms.


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)

Chemical structure of caffeic acid (CA).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Chemical structure of caffeic acid (CA).
Mentions: Caffeic acid (CA) is one of the major water-soluble components of Radix Salvia miltiorrhiza. The chemical structure of CA is illustrated in Fig. 1. Accumulating evidence has confirmed that CA has potent antioxidant and anti-inflammatory activities1617. Previous studies showed that CA can inhibit the cyclooxygenase activity and the adhesion protein P-selectin expression in platelets in vitro181920. A recent study demonstrated the potential of CA to inhibit collagen-induced platelet aggregation via cAMP-dependent inositol-1,4,5-trisphosphate receptor phosphorylation21. However, little is known regarding the role of CA in platelet mediated thrombus generation in vivo, and the mechanism thereby the influence of CA on ADP-induced platelet activation has not been fully understood. The aim of this study was to examine the effects of CA on platelet mediated thrombosis in mouse cerebral microvessels and characterize the underlying mechanisms.

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