Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.
School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien 970, Taiwan.
Molecules. 2022 Jun 23;27(13):4054. doi: 10.3390/molecules27134054.
Coumarin was first discovered in Tonka bean and then widely in other plants. Coumarin has an anticoagulant effect, and its derivative, warfarin, is a vitamin K analogue that inhibits the synthesis of clotting factors and is more widely used in the clinical treatment of endovascular embolism. At present, many artificial chemical synthesis methods can be used to modify the structure of coumarin to develop many effective drugs with low toxicity. In this study, we investigated the effects of six coumarin derivatives on the platelet aggregation induced by adenosine diphosphate (ADP). We found that the six coumarin derivatives inhibited the active form of GPIIb/IIIa on platelets and hence inhibit platelet aggregation. We found that 7-hydroxy-3-phenyl 4H-chromen-4-one (7-hydroxyflavone) had the most severe effect. In addition, we further analyzed the downstream signal transduction of the ADP receptor, including the release of calcium ions and the regulation of cAMP, which were inhibited by the six coumarin derivatives selected in this study. These results suggest that coumarin derivatives inhibit coagulation by inhibiting the synthesis of coagulation factors and they may also inhibit platelet aggregation.
香豆素最初在丁子香豆中被发现，然后在其他植物中广泛存在。香豆素有抗凝作用，其衍生物华法林是一种维生素 K 类似物，能抑制凝血因子的合成，在血管内栓塞的临床治疗中应用更为广泛。目前，有许多人工化学合成方法可以用来修饰香豆素的结构，开发出许多毒性低、效果好的药物。在这项研究中，我们研究了六种香豆素衍生物对二磷酸腺苷（ADP）诱导的血小板聚集的影响。我们发现，这六种香豆素衍生物抑制了血小板上 GPIIb/IIIa 的活性形式，从而抑制了血小板聚集。我们发现 7-羟基-3-苯基 4H-色烯-4-酮（7-羟基黄酮）的抑制作用最强。此外，我们还进一步分析了 ADP 受体的下游信号转导，包括钙离子的释放和 cAMP 的调节，这六种香豆素衍生物都能抑制其作用。这些结果表明，香豆素衍生物通过抑制凝血因子的合成来抑制凝血，同时也可能抑制血小板聚集。
