At the interface of antioxidant signalling and cellular function: Key polyphenol effects

Abstract

The hypothesis that dietary (poly)phenols promote well-being by improving chronic disease-risk biomarkers, such as endothelial dysfunction, chronic inflammation and plasma uric acid, is the subject of intense current research, involving human interventions studies, animal models and in vitro mechanistic work. The original claim that benefits were due to the direct antioxidant properties of (poly)phenols has been mostly superseded by detailed mechanistic studies on specific molecular targets. Nevertheless, many proposed mechanisms in vivo and in vitro are due to modulation of oxidative processes, often involving binding to specific proteins and effects on cell signalling. We review the molecular mechanisms for 3 actions of (poly)phenols on oxidative processes where there is evidence in vivo from human intervention or animal studies. (1) Effects of (poly) phenols on pathways of chronic inflammation leading to prevention of some of the damaging effects associated with the metabolic syndrome. (2) Interaction of (poly)phenols with endothelial cells and smooth muscle cells, leading to effects on blood pressure and endothelial dysfunction, and consequent reduction in cardiovascular disease risk. (3) The inhibition of xanthine oxidoreductase leading to modulation of intracellular superoxide and plasma uric acid, a risk factor for developing type 2 diabetes.

Keywords: Endothelial function; Flavonoid; Inflammation; Phenolic acid; Uric acid.

Figure 1

Selected metabolic pathways involved in vasoconstriction and vasodilation where there is evidence for the action of (poly)phenols. sGC, soluble guanylyl cyclase; VEGFR, vascular endothelial growth factor receptor; VEGF, vascular endothelial growth factor; SOD, superoxide dismutase; eNOS, endothelial nitric oxide synthase. Thin arrows show direct reactions, dotted arrows indicate pathway with multiple reactions/interactions, and a dot‐dash line indicates movement of molecules.

Figure 2

Selected metabolic pathways leading to generation of uric acid in the liver. ADA, adenosine deaminase; PNP, purine nucleoside phosphorylase; FK, fructokinase; ENT2, SLC29A2; GLUT5, SLC2A5; GLUT9, SLC2A9. Thin arrows show direct reactions, dotted arrows indicate pathway with multiple reactions/interactions, and a dot‐dash line indicates movement of molecules.