Phytochemicals and endothelial dysfunction: recent advances and perspectives

Endothelial dysfunction (impaired vasodilation, prothrombotic, proinflammatory and prooxidant states) is involved in the development of cardiovascular diseases (atherosclerosis, hypertension, heart failure, stroke) and vascular complications of diabetes mellitus. Reduced production of endothelium-derived relaxing factors, increased release of endothelium-derived constricting factors, prothrombotic molecules and inflammatory mediators, upregulation of growth factors and adhesion molecules play a crucial role in the development and progression of endothelial dysfunction. Phytochemicals belonging to different chemical classes (alkaloids, flavonoids, isoflavonoids, phenolic acids, terpenoids) were reported to prevent and/or reverse endothelial dysfunction in different experimental models. Many of them showed a multitarget activity which is a great advantage in tackling endothelial dysfunction and thereby, they may serve as lead compounds for novel drug development. Salvianolic acid B, caffeic, chlorogenic, ferulic and rosmarinic acids, resveratrol, luteolin are only some examples of phytochemicals modulating multiple mechanisms associated with endothelial dysfunction. Obviously, extensive clinical trials are needed to confirm the efficacy of phytochemicals in improving endothelial function and also their safety. In addition, formulation strategies to enhance bioavailability and afford an endothelium-targeted delivery should be explored.