Intestinal and hepatic glucuronidation of flavonoids

Flavonoids are polyphenolic phytochemicals present extensively in our daily diets, beverages, medicinal plants, and herbal remedies. The diverse biological effects of flavonoids have aroused great interest in scientists. In the past decade, various studies demonstrated extensive conjugate metabolisms, especially glucuronidation, of flavonoids in intestine and liver implying an important role of the glucuronidation in causing low oral bioavailability of flavonoids. The present article aims to review the up-to-date information on the studies of the first-pass metabolism, in particular glucuronidation, of flavonoids in the gastrointestinal tract and the liver, and also the isoformic enzymes involved in the metabolism and disposition of flavonoids. In addition, the role of efflux transporters, enterohepatic circulation, and enteric cycling in the disposition of flavonoid glucuronides has also been illustrated. Despite low oral bioavailabilities of the parent compounds, flavonoids and some of their bioactive phase II conjugates may accumulate adequate amount in the body to produce their pharmacological activities. Further investigation on the correlation between the accumulated concentrations of flavonoids and their pharmacological activities after their repeated oral administration is warranted.