Interactions of polyphenolic compounds with drug disposition and metabolism

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.