Polyphenols are a heterogeneous class of compounds that include several hydrosoluble
antioxidants useful in food preservation and claimed as health promoting agents. However, a number of studies in recent years have demonstrated that this class of compounds also contains powerful
xenobiotics and cell stress inducers, which in turn elicit responses of defence and adaptation of the gastrointestinal tract and possibly of other organs. These responses investigated both in vitro and in vivo include the modulation of various groups of metabolic and stress genes, as well as effects on the expression and activity of detoxification systems, such as
drug metabolising
enzymes (
DMEs),
antioxidant and phase II
enzymes, and transporter
proteins. Such effects have been extensively interpreted as useful in that they can produce greater protection against
xenobiotics and "cellular stresses" of endogenous and exogenous origin, and may indicate a mechanism for the preventive role that
polyphenols are believed to play against the degenerative events of aging and
chronic diseases. Conversely, these gene induction effects and the interaction with detoxification responses can have negative consequences by the generation of more reactive and harmful intermediates, and modified bioavailability and in vivo bioactivity of drugs, nutrients and the same
polyphenols. This paper provides an overview of the recent literature on the mechanisms that govern biochemical and molecular responses to polyphenolic compounds relevant to
drug metabolism, disposition and therapeutic efficacy.