Chlorogenic Acid Inhibits Human Platelet Activation and Thrombus Formation

被引:91
作者
Fuentes, Eduardo [1 ,2 ]
Caballero, Julio [3 ]
Alarcon, Marcelo [1 ,2 ]
Rojas, Armando [4 ]
Palomo, Ivan [1 ,2 ]
机构
[1] Univ Talca, Dept Clin Biochem & Immunohematol, Interdisciplinary Excellence Res Program Hlth Agi, Fac Hlth Sci, Talca, Chile
[2] CONICYT Reg, CEAP, Gore Maule, Talca, Chile
[3] Univ Talca, Fac Engn Bioinformat, Ctr Bioinformat & Mol Simulat, Talca, Chile
[4] Catholic Univ Maule, Fac Med, Biomed Res Labs, Talca, Chile
关键词
P-SELECTIN EXPRESSION; PROTEIN-KINASE-A; ADENOSINE RECEPTOR; INCREASES; THERAPY; ASPIRIN; DOCKING; BINDING; COFFEE;
D O I
10.1371/journal.pone.0090699
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Chlorogenic acid is a potent phenolic antioxidant. However, its effect on platelet aggregation, a critical factor in arterial thrombosis, remains unclear. Consequently, chlorogenic acid-action mechanisms in preventing platelet activation and thrombus formation were examined. Methods and Results: Chlorogenic acid in a dose-dependent manner (0.1 to 1 mmol/L) inhibited platelet secretion and aggregation induced by ADP, collagen, arachidonic acid and TRAP-6, and diminished platelet firm adhesion/aggregation and platelet-leukocyte interactions under flow conditions. At these concentrations chlorogenic acid significantly decreased platelet inflammatory mediators (sP-selectin, sCD40L, CCL5 and IL-1 beta) and increased intraplatelet cAMP levels/PKA activation. Interestingly, SQ22536 (an adenylate cyclase inhibitor) and ZM241385 (a potent A(2A) receptor antagonist) attenuated the antiplatelet effect of chlorogenic acid. Chlorogenic acid is compatible to the active site of the adenosine A(2A) receptor as revealed through molecular modeling. In addition, chlorogenic acid had a significantly lower effect on mouse bleeding time when compared to the same dose of aspirin. Conclusions: Antiplatelet and antithrombotic effects of chlorogenic acid are associated with the A(2A) receptor/adenylate cyclase/cAMP/PKA signaling pathway.
引用
收藏
页数:13
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