An alternative pathway to widespread health benefits of dietary polyphenols: The nitrate-nitrite-nitric oxide pathway in the gut

Abstract

Dietary polyphenols are redox active compounds endowed with recognized health benefits. Their in vivo impact needs to be addressed in connection with a sequence of reactions intrinsically related to the biological compartments that, after consumption in the diet, the alimentary bolus travels through. In this regard, it has been recognized that the structural modifications suffered in the gut and during absorption alter the kinetic and thermodynamic properties supportive of the well-known antioxidant properties in vitro. The chemical, biophysical and biological properties of their metabolites are, in most cases, quite different from the ones of the parent molecules. Thus, the current view for the wide-range effects of dietary polyphenols considers their bioavailability and the potential effects of metabolites derived from the original structures consumed in the diet. Few years ago we have shown that dietary polyphenols and dietary nitrite interact in the human stomach yielding a burst of nitric oxide (NO) in a process encompassing the one electron reduction of nitrite by polyphenols [1]. In turn, NO, a ubiquitous cell messenger, exert not only local but more widespread effects. In fact, at acidic gastric pH, dietary polyphenols, in the form they are conveyed in foods and at high concentration, promote nitrite reduction to NO but also embark in a complex network of chemical reactions to produce higher nitrogen oxides with signaling functions, namely by inducing post-translational modifications. Modified endogenous molecules, such as nitrated proteins and lipids, acquire important physiological functions via the modulation of redox signaling pathways. Systemic effects of NO such as modulation of vascular tone, mucus production in the gut and protection against ischemia-reperfusion injury might, in this sense, triggered by dietary polyphenols. This rises the notion that bypassing gut metabolization and absorption, the redox and kinetic properties of original polyphenolic structures trigger wide-spread biological effects via the nitrate:nitrite:nitric oxide pathway. This notion will be herein experimentally supported and discussed.