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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 inhibits ADP-induced platelet aggregation.Platelets were preincubated with or without CA in the presence of CaCl2 (1 mM) at 37 °C for 20 min followed by the addition of ADP (20 μM). The cells were then incubated for 6 min. After incubation with the agonists, platelet aggregation was quantified and expressed as a percentage. Data are expressed as means ± SEM (n = 10). *p < 0.05 vs control group, #p < 0.05 vs ADP group.
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f4: CA inhibits ADP-induced platelet aggregation.Platelets were preincubated with or without CA in the presence of CaCl2 (1 mM) at 37 °C for 20 min followed by the addition of ADP (20 μM). The cells were then incubated for 6 min. After incubation with the agonists, platelet aggregation was quantified and expressed as a percentage. Data are expressed as means ± SEM (n = 10). *p < 0.05 vs control group, #p < 0.05 vs ADP group.

Mentions: ADP is a well-known agonist for platelet aggregation and thrombus formation. To verify the effect of CA on platelet activation, we performed an in vitro mouse platelet aggregation test. As shown in Fig. 4, CA (5–100 μM) revealed a dose-dependent inhibition of platelet aggregation caused by ADP (20 μM). Furthermore, argatroban and picotamide were used to exclude the possibility that the effect of CA on ADP-induced platelet aggregation was due to the inhibition of thrombin secretion or thromboxane A2 (TXA2) generation. CA inhibited ADP-induced platelet aggregation as well regardless of the presence of argatroban or picotamide, suggesting a thrombin - and TXA2-independent effect of CA (Supplemental Figs 1 and 2).


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 inhibits ADP-induced platelet aggregation.Platelets were preincubated with or without CA in the presence of CaCl2 (1 mM) at 37 °C for 20 min followed by the addition of ADP (20 μM). The cells were then incubated for 6 min. After incubation with the agonists, platelet aggregation was quantified and expressed as a percentage. 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

f4: CA inhibits ADP-induced platelet aggregation.Platelets were preincubated with or without CA in the presence of CaCl2 (1 mM) at 37 °C for 20 min followed by the addition of ADP (20 μM). The cells were then incubated for 6 min. After incubation with the agonists, platelet aggregation was quantified and expressed as a percentage. Data are expressed as means ± SEM (n = 10). *p < 0.05 vs control group, #p < 0.05 vs ADP group.
Mentions: ADP is a well-known agonist for platelet aggregation and thrombus formation. To verify the effect of CA on platelet activation, we performed an in vitro mouse platelet aggregation test. As shown in Fig. 4, CA (5–100 μM) revealed a dose-dependent inhibition of platelet aggregation caused by ADP (20 μM). Furthermore, argatroban and picotamide were used to exclude the possibility that the effect of CA on ADP-induced platelet aggregation was due to the inhibition of thrombin secretion or thromboxane A2 (TXA2) generation. CA inhibited ADP-induced platelet aggregation as well regardless of the presence of argatroban or picotamide, suggesting a thrombin - and TXA2-independent effect of CA (Supplemental Figs 1 and 2).

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