Flavonoids are naturally occurring polyphenols, which are widely taken in diets, supplements and herbal medicines. Epidemiological
studies have shown a flavonoid-rich diet is associated with the decrease in incidence of a range of diseases. Pharmacological
evidences also reveal flavonoids display anti-oxidant, anti-allergic, anti-cancer, anti-inflammatory, anti-microbial and anti-diarrheal activities.
Therefore, it is critical to study the biotransformation and disposition of flavonoids in human. This review summarizes the major
metabolism pathways of flavonoids in human. First, lactase-phlorizin hydrolase (LPH) and human intestinal microflora mediate the hydrolysis
of flavonoid glycosides, which is recognized as the first and determinant step in the absorption of flavonoids. Second, phase II
metabolic enzymes (UGTs, SULTs and COMT) dominate the metabolism of flavonoids in vivo. UGTs are the most major contributors,
followed by SULTs and COMT. By contrast, phase I metabolism pathway mediated by CYPs only plays a minor role. Third, the coupling
of transporters (such as BCRP and MRPs) and phase II enzymes (UGTs and SULTs) plays an important role in the disposition of
flavonoids, especially in the enteroenteric and enterohepatic circulations. Thus, all the above factors should be taken into consideration
when studying pharmacokinetics of flavonoids. Here we describe a comprehensive metabolism profile of flavonoids, which will enhance
our understanding of the mechanisms underlying the disposition and pharmacological effects of flavonoids in vivo.