Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Department of Pharmacology and Toxicology, Heyrovskeho 1 203, 500 05 Hradec Kralove, Czech Republic.
Curr Top Med Chem. 2015;15(9):830-49. doi: 10.2174/1568026615666150220112437.
Coumarins are a large group of substances, primarily of plant origin. Like their more intensively examined congeners flavonoids, many of them are antioxidants. Although such properties may be advantageous in cardiovascular diseases, it has been shown that coumarins exhibit direct effects on the cardiovascular system which are not based on antioxidant activity. The most common example is the well-known drug warfarin, a synthetic compound derived from natural dicoumarol. Moreover, other coumarins have been shown to possess antiplatelet and vasodilatory potential. Interestingly, the former effect may be mediated by the inhibition of various pathways leading to platelet aggregation, their differing effects on those pathways being due to structural differences between the various coumarins. Conversely, their vasodilatory potential is linked in the majority of cases to the inhibition of increases in intracellular calcium concentration in vascular smooth muscle cells, and in several coumarins also to NO-mediated vasodilatation. Available data on both activities are summarized in this review. At the end of this review, relevant data are provided from a few studies testing the in vivo effects of coumarins on major cardiovascular diseases; the clinical use of warfarin and other coumarin anticoagulants, as well as the limited data on the clinical use of coumarins in chronic venous insufficiency and the possible toxicological effects of coumarins.
香豆素是一大类物质，主要来源于植物。与它们更受关注的同类黄酮一样，其中许多具有抗氧化作用。尽管这些特性在心血管疾病中可能是有益的，但已经表明香豆素对心血管系统具有直接作用，而这些作用不是基于抗氧化活性。最常见的例子是众所周知的药物华法林，这是一种从天然双香豆素衍生而来的合成化合物。此外，其他香豆素已被证明具有抗血小板和血管扩张作用。有趣的是，前者的作用可能是通过抑制导致血小板聚集的各种途径来介导的，其对这些途径的不同作用归因于各种香豆素之间的结构差异。相反，它们的血管扩张潜力在大多数情况下与抑制血管平滑肌细胞内钙浓度的增加有关，在几种香豆素中也与 NO 介导的血管扩张有关。本综述总结了这两种活性的现有数据。在本综述的最后，提供了一些研究的相关数据，这些研究测试了香豆素对主要心血管疾病的体内作用；华法林和其他香豆素抗凝剂的临床应用，以及香豆素在慢性静脉功能不全中的临床应用的有限数据和香豆素的可能毒理学作用。
