Phenolic extracts from whole wheat biofortified bread dampen overwhelming inflammatory response in human endothelial cells and monocytes: major role of VCAM- 1 and CXCL-10

Purpose The aim of the study was to evaluate the vascular health properties of extracts from biofortified bread, obtained byadding different durum wheat milling by-products rich in phenolic compounds, by analyzing their effects on overwhelminginflammatory response in endothelial cells and monocytes, two main players of atherogenesis.Methods Human umbilical vein endothelial cells or U937 monocytes were incubated with increasing concentrations (1, 5, 10ug/mL) of biofortified bread polyphenol extracts or corresponding pure phenolic acids before stimulation with lipopolysaccharide(LPS). We analyzed the endothelial-monocyte adhesion and related endothelial adhesion molecules. The expressionof chemokines and pro-inflammatory cytokines was also measured in LPS-stimulated endothelial cells and monocytes aswell as intracellular oxidative stress.Results Biofortified bread extracts inhibited monocyte adhesion to LPS-stimulated endothelial cells, in a concentrationdependentmanner by reducing mainly endothelial VCAM-1 expression. Phenolic acid extracts contained in 10 mg biofortifiedbread downregulated the LPS-induced expression of chemokines MCP-1, M-CSF, and CXCL-10 as well as pro-inflammatorycytokines TNF-alfa and IL-1beta, in endothelial cells and monocytes, with CXCL-10 as the most reduced inflammatory mediator.Among phenolic acids of biofortified bread, ferulic, sinapic, and p-coumaric acids significantly inhibited the LPS-stimulatedCXCL-10 expression in vascular cells. The reduced pro-inflammatory response was related to a slightly but significant reductionof intracellular oxidative stress.Conclusions Our findings suggest the bread biofortified with selected durum wheat milling by-products as a source of phenolicacids with multiple anti-inflammatory and anti-atherosclerotic properties, which could help to counteract or preventinflammatory vascular diseases.