Regulation of cellular signals from nutritional molecules: a specific role for phytochemicals, beyond antioxidant activity

Phytochemicals (PhC) are a ubiquitous class of plant secondary metabolites. A "recommended" human diet should warrant a high proportion of energy from fruits and vegetables, therefore providing, among other factors, a huge intake of PhC, in general considered "health promoting" by virtue of their antioxidant activity and positive modulation, either directly or indirectly, of the cellular and tissue redox balance. Diet acts through multiple pathways and the association between the consumption of specific food items and the risk of degenerative diseases is extremely complex. Recent literature suggests that molecules having a chemical structure compatible with a putative antioxidant capacity can actually "perform" activities and roles independent of such capacity, interacting with cellular functions at different levels, such as affecting enzyme activities, binding to membrane or nuclear receptors as either an elective ligand or a ligand mimic. Inductive or signaling effects may occur at concentrations much lower than that required for effective antioxidant activity. Therefore, the "antioxidant hypothesis" is to be considered in some cases an intellectual "shortcut" possibly biasing the real understanding of the molecular mechanisms underlying the beneficial effects of various classes of food items. In the past few years, many exciting new indications elucidating the mechanisms of polyphenols have been published. Here, we summarize the current knowledge of the mechanisms by which specific molecules of nutritional interest, and in particular polyphenols, play a role in cellular response and in preventing pathologies. In particular, their direct interaction with nuclear receptors and their ability to modulate the activity of key enzymes involved in cell signaling and antioxidant responses are presented and discussed. (c) 2008 Elsevier Inc. All rights reserved.