Preventive effect of cocoa flavanols against glucotoxicity-induced vascular inflammation in the arteria of diabetic rats and on the inflammatory process in TNF-α-stimulated endothelial cells

Abstract

Hyperglycaemia induces a vascular inflammatory process that is a critical event in cardiovascular disease in type 2 diabetes. Cocoa and its flavanols have been widely investigated for its antioxidant and anti-inflammatory properties, and several clinical and pre-clinical studies support their vascular benefits. However, the effects of cocoa flavanols on vascular inflammation in diabetes remains to be elucidated. Herein, we evaluated the anti-inflammatory effect of a cocoa-rich diet on the aortas of Zucker diabetic fatty (ZDF) rats. Moreover, the potential role of flavanol-derived colonic metabolites to modulate the adhesion and inflammatory processes were also evaluated using TNF-α-stimulated endothelial cells. Results demonstrate that cocoa attenuates the levels of phospho-p65-nuclear factor-kappaB (NF-κB) and the expression of inflammatory factors including intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and inducible nitric oxide synthase in the aortas of ZDF rats. Experiments with endothelial cells further confirm that a mix of flavanol-derived colonic metabolites effectively down-regulate the levels of p-p65-NF-κB and the cell adhesion molecules ICAM-1 and VCAM-1, preventing thus the increase of monocyte-endothelial adhesion induced by TNF-α. These novel data provide the first evidence of the relevant role of cocoa and their flavanol-derived metabolites to avoid the development of endothelial inflammation and diabetic complications.