Bioavailability and molecular activities of anthocyanins as modulators of endothelial function

Abstract

Anthocyanins (AC) are water-soluble natural pigments found in various parts of higher plants. Despite their limited oral bioavailability and very low post-absorption plasma concentrations, the dietary consumption of these pigments has been proposed to be associated with a significant protection against several human pathological conditions, including cardiovascular diseases. Many studies highlighted that some health benefits of AC localize in particular at endothelium level, contributing to vascular homeostasis and also to the control of angiogenesis, inflammation, and platelet aggregation. This review reports and comments on the large existing literature addressing the molecular mechanisms that, beyond the antioxidant properties, may have a significant role in the effects of AC and AC-rich foods on vessel endothelium. Among these, AC have been reported to prevent peroxynitrite-mediated endothelial dysfunction in endothelial cells (ECs), thanks to their capability to modulate the expression and activity of several enzymes involved in NO metabolism. Furthermore, evidence indicates that AC can prevent the expression of adhesion molecules and the adhesion of monocytes to ECs challenged by pro-inflammatory agents. Overall, the activity of AC could be associated with the ability to elicit cell adaptive responses involving the transcription factor Nrf2 by affecting the "nucleophilic tone" of the organism. This review confirms the importance of specific nutritional molecules for human health and suggests new avenues for nutrition-based interventions to reduce the risk of cardiovascular disease in the population.

Fig. 1

Endothelial cells functions. Endothelium plays a critical role in maintaining vascular homeostasis. ECs function as a barrier regulating the flow of nutrient substances and different biologically active molecules. The endothelium is essential in controlling the passage of fluid into tissue, in modulating cellular trafficking and coagulation, and in regulating blood pressure. The endothelium also plays a key role in the regulation of immune responses, and the endothelial cell layer serves as the gateway for the entry of leukocytes into tissue in response to inflammatory stimuli. CAMs cell adhesion molecules, NO nitric oxide, PGI2 prostacyclin, TXA2 thromboxane A2, ET endothelin, ROS reactive oxygen species, tPA tissue plasminogen activator, PAI-1 plasminogen activator inhibitor 1, PAF platelet-activating factor, TF tissue factor

Fig. 2

Effects of AC in vascular endothelium. Anthocyanins are potent inducers of the endothelial formation of NO involving different intracellular signaling pathways. Furthermore, AC are able to modulate pro-inflammatory pathway by inhibiting ROS and the redox-sensitive transcription factor NF-κB. Indirect mechanisms involved in ROS scavenging ability of AC could be also linked to acute activation of antioxidant and detoxifying enzymes modulated by Nrf2 transcription factor. ROS reactive oxygen species, PI3K phosphatidylinositol 3-kinase, MAPK mitogen-activated protein kinases, ERK1/2 extracellular regulated kinase 1 and 2, Akt protein kinase B, LDL-ox oxidized low density lipoprotein, TNF-a tumor necrosis factor a, eNOS endothelial NO synthase, NO nitric oxide, ER estrogen receptor, Cav-1 caveolin-1, sGC soluble guanylyl cyclase, GTP guanosine-5′-triphosphate, cGMP cyclic guanosine monophosphate, NQO1 NAD(P)H:quinone oxidoreductase-1, HO-1 heme oxygenase-1, KEAP1 kelch-like-ECH-associated protein 1, Nrf2 nuclear factor erythroid-2 (NF-E2)-related factor 2