title: Metabolism of flavonoids in human: a comprehensive review.
abstract: 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.
authors.forename: Zhongjian
authors.initials: Z
authors.lastname: Chen
authors.forename: Shirui
authors.initials: S
authors.lastname: Zheng
authors.forename: Liping
authors.initials: L
authors.lastname: Li
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China. hdjiang@zju.edu.cn.
authors.forename: Huidi
authors.initials: H
authors.lastname: Jiang
mesh_terms: D002394:Catechol O-Methyltransferase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005419:Flavonoids / Q000493:pharmacokinetics*; D014453:Glucuronosyltransferase / Q000378:metabolism; D006027:Glycosides / Q000493:pharmacokinetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism
chemical_list: D005419:Flavonoids; D006027:Glycosides; D003577:Cytochrome P-450 Enzyme System; D002394:Catechol O-Methyltransferase; D014453:Glucuronosyltransferase; D015238:Sulfotransferases