绿原酸抑制人类血小板活化和血栓形成。
Chlorogenic acid inhibits human platelet activation and thrombus formation.
作者信息
Fuentes Eduardo, Caballero Julio, Alarcón Marcelo, Rojas Armando, Palomo Iván
机构信息
Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca, Chile; Centro de Estudios en Alimentos Procesados (CEAP), CONICYT-Regional, Gore Maule, Talca, Chile.
Center for Bioinformatics and Molecular Simulations, Faculty of Engineering in Bioinformatics, Universidad de Talca, Talca, Chile.
出版信息
PLoS One. 2014 Mar 5;9(3):e90699. doi: 10.1371/journal.pone.0090699. eCollection 2014.
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-1β) and increased intraplatelet cAMP levels/PKA activation. Interestingly, SQ22536 (an adenylate cyclase inhibitor) and ZM241385 (a potent A2A receptor antagonist) attenuated the antiplatelet effect of chlorogenic acid. Chlorogenic acid is compatible to the active site of the adenosine A2A 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 A2A receptor/adenylate cyclase/cAMP/PKA signaling pathway.
背景
绿原酸是一种有效的酚类抗氧化剂。然而，其对血小板聚集（动脉血栓形成的关键因素）的影响仍不清楚。因此，研究了绿原酸在预防血小板活化和血栓形成中的作用机制。
方法与结果
绿原酸以剂量依赖性方式（0.1至1 mmol/L）抑制由ADP、胶原、花生四烯酸和TRAP-6诱导的血小板分泌和聚集，并在流动条件下减少血小板牢固黏附/聚集以及血小板-白细胞相互作用。在这些浓度下，绿原酸显著降低血小板炎症介质（可溶性P-选择素、可溶性CD40配体、CCL5和白细胞介素-1β）并提高血小板内cAMP水平/蛋白激酶A（PKA）活性。有趣的是，SQ22536（一种腺苷酸环化酶抑制剂）和ZM241385（一种有效的A2A受体拮抗剂）减弱了绿原酸的抗血小板作用。通过分子模拟显示，绿原酸与腺苷A2A受体的活性位点相匹配。此外，与相同剂量的阿司匹林相比，绿原酸对小鼠出血时间的影响显著更低。
结论
绿原酸的抗血小板和抗血栓作用与A2A受体/腺苷酸环化酶/cAMP/PKA信号通路相关。
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