Pharmacology Unit, Biomedical Sciences Department, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
Molecules. 2021 May 19;26(10):3036. doi: 10.3390/molecules26103036.
Atherosclerotic cardiovascular disease is the leading cause of death in developed countries. Therefore, there is an increasing interest in developing new potent and safe antiplatelet agents. Coumarins are a family of polyphenolic compounds with several pharmacological activities, including platelet aggregation inhibition. However, their antiplatelet mechanism of action needs to be further elucidated. The aim of this study is to provide insight into the biochemical mechanisms involved in this activity, as well as to establish a structure-activity relationship for these compounds. With this purpose, the antiplatelet aggregation activities of coumarin, esculetin and esculin were determined in vitro in human whole blood and platelet-rich plasma, to set the potential interference with the arachidonic acid cascade. Here, the platelet COX activity was evaluated from 0.75 mM to 6.5 mM concentration by measuring the levels of metabolites derived from its activity (MDA and TXB), together with colorimetric assays performed with the pure recombinant enzyme. Our results evidenced that the coumarin aglycones present the greatest antiplatelet activity at 5 mM and 6.5 mM on aggregometry experiments and inhibiting MDA levels.
动脉粥样硬化性心血管疾病是发达国家的主要死亡原因。因此，人们越来越关注开发新的有效且安全的抗血小板药物。香豆素是一类具有多种药理活性的多酚类化合物，包括抑制血小板聚集。然而，其抗血小板作用机制仍需进一步阐明。本研究旨在深入了解这一活性涉及的生化机制，并为这些化合物建立构效关系。为此，我们在人全血和富含血小板的血浆中测定了香豆素、秦皮素和秦皮乙素的抗血小板聚集活性，以确定其对花生四烯酸级联的潜在干扰。在此，通过测量其活性产生的代谢物（MDA 和 TXB）的水平，以及使用纯重组酶进行比色测定，评估血小板 COX 活性在 0.75 mM 至 6.5 mM 浓度范围内的变化。我们的结果表明，在聚集实验和抑制 MDA 水平方面，香豆素苷元在 5 mM 和 6.5 mM 时具有最大的抗血小板活性。
