Novel molecular mechanisms by which ginger extract reduces the inflammatory stress in TNFα – activated human endothelial cells; decrease of Ninjurin-1, TNFR1 and NADPH oxidase subunits expression

[Display omitted] •GEx diminishes MCP-1, VCAM-1 and monocyte adhesion in TNFα-exposed HEC.•GEx anti-inflammatory action was correlated with the decrease of Ninj-1 and TNFR1.•GEx decreases intracellular RAGE expression and increases sRAGE levels.•GEx decrease ROS by reducing p22phox and NOX4 and activating Nrf2/HO-1 axis. Dysfunction of endothelial cells (EC) is important for atherosclerosis progression. The aim of this study was to evaluate the potential of ginger extract (GEx), 6-gingerol (6-G) and 6-shogaol (6-Sh) to reverse EC dysfunction and to investigate its mechanism of action, using cultured human EC incubated with TNFα. The results showed that GEx decreases monocyte chemoattractant protein-1, vascular cell adhesion molecule-1 and monocyte adhesion. This decrease was associated with the: (1) decrease of ninjurin-1 expression; (2) reduction of TNFα receptor1 and of the receptor for advanced glycation end-products expression (RAGE), in parallel with the increase of soluble RAGE; (3) decrease of NADPH oxidase subunits expression; (4) activation of antioxidant Nrf2 and heme oxygenase-1, and (5) inhibition of NF-kB. The benefic effects of 6-G and 6-Sh were weaker than those of GEx (GEx > 6-Sh > 6-G). In conclusion, GEx might be a promising alternative to ameliorate disorders in which oxidative stress and inflammation are important.