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

Abstract

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.