CNR Institute of Clinical Physiology, Via G. Moruzzi, 1, 56124 Pisa, Italy.
Department of Pharmacy, University of Pisa, Via Bonanno, 6, 56126 Pisa, Italy.
Food Chem. 2015 May 15;175:494-9. doi: 10.1016/j.foodchem.2014.12.005. Epub 2014 Dec 16.
We investigated the ability of quercetin and apigenin to modulate platelet activation and aggregation, and compared the observed efficacy with that displayed by their synthetic analogues 2-phenyl-4H-pyrido[1,2-a]pyrimidin-4-ones, 1-4, and 2,3-diphenyl-4H-pyrido[1,2-a]pyrimidin-4-ones, 5-7. Platelet aggregation was explored through a spectrophotometric assay on platelet-rich plasma (PRP) treated with the thromboxane A2 mimetic U46619, collagen and thrombin in presence/absence of various bioisosteres of flavonoids (12.5-25-50-100 μM). The platelet density, (mean platelet component, MPC), was measured by the Advia 120 Hematology System as a marker surrogate of platelet activation. The induced P-selectin expression, which reflects platelet degranulation/activation, was quantified by flow cytometry on PRP. Our synthetic compounds modulated significantly both platelet activation and aggregation, thus turning out to be more effective than the analogues quercetin and apigenin when tested at a concentration fully consistent with their use in vivo. Accordingly, they might be used as food supplements to increase the efficacy of natural flavonoids.
我们研究了槲皮素和芹菜素调节血小板活化和聚集的能力，并将观察到的效果与它们的合成类似物 2-苯基-4H-吡啶并[1,2-a]嘧啶-4-酮、1-4 和 2,3-二苯基-4H-吡啶并[1,2-a]嘧啶-4-酮、5-7 进行了比较。通过在富含血小板的血浆（PRP）中用血栓烷 A2 模拟物 U46619、胶原蛋白和凝血酶处理，并用黄酮类生物等排体（12.5-25-50-100 μM）进行分光光度法测定血小板聚集。血小板密度（平均血小板成分，MPC）通过 Advia 120 血液学系统作为血小板活化的标志物进行测量。通过流式细胞术在 PRP 上定量诱导的 P-选择素表达，反映血小板脱颗粒/活化。我们的合成化合物显著调节了血小板的活化和聚集，因此在与体内使用一致的浓度下，其效果比类似物槲皮素和芹菜素更显著。因此，它们可用作食品补充剂，以提高天然类黄酮的功效。
