An update on polyphenol disposition via coupled metabolic pathways

ABSTRACTIntroduction: Polyphenols, which are widely distributed in plants and the human diets, are known to have numerous biological activities. However, the low bioavailability of polyphenols is mediated by coupled metabolic pathways.Areas covered: The key role of the interplay between drug metabolic enzymes (DMEs) and efflux transporters (ETs), nuclear receptors (NRs), and intestinal microflora in the disposition of polyphenols is summarized.Expert opinion: ETs are shown to act as a ‘revolving door’, facilitating and/or controlling cellular polyphenol glucuronide/sulfate excretion. Elucidating the mechanisms underlying the glucuronidation/sulfation–transport interplay and structure-activity relationships (SAR) of glucuronide/sulfate efflux by an ET is important. Some new physiologically based pharmacokinetic (PBPK) models could be developed to predict the interplay between glucuronides/sulfates and ETs. Additionally, the combined actions of uridine-5′-diphosphate glucuronosyltransferases, ETs, and intes...