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.

Dietary flavonoids advance timing of moult but do not affect redox status of juvenile blackbirds (Turdus merula)

“…In contrast to in vitro studies, it is indeed possible that flavonoids do not directly modulate antioxidant activity in vivo, as they appear to be extensively metabolized and their metabolites may not be very effective as free radical scavengers (Chen et al, 2014;Rodriguez-Mateos et al, 2014). However, flavonoids and their metabolites may promote upregulation of antioxidant enzymes such as catalase, glutathione peroxidase and superoxide dismutase, whose biological activity may efficiently contribute to prevent oxidative insults (Halliwell and Gutterridge, 2003).…”

UPLC-Q-TOF/MS-based screening and identification of two major bioactive components and their metabolites in normal and CKD rat plasma, urine and feces after oral administration of Rehmannia glutinosa Libosch extract

“…Based on the above reasons, we proposed the change of metabolic profiles of catalpol and acteoside in CKD rats compared with that in normal rats after oral administration of R. glutinosa extract might be due to the reduced metabolic enzymes in the CKD state. Additionally, it has been widely reported that glycosides in orally administrated medicines usually could be metabolized by intestinal bacteria before absorption into blood [26][27][28]. Marked alteration of the colonic bacterial flora was also observed in humans and animals with advanced CKD [29].…”

Cytotoxic action of methylquercetins in human lung adenocarcinoma cells

“…One reason for this is the very limited commercial availability of metabolites for experimental testing. There are three major types of metabolic derivatives of flavonoids formed as a consequence of enzymatic conjugation with methyl-, sulfate-or glycuronyl groups in the small intestine and liver catalyzed by COMT, sulfotransferase (SULT) or UDP-glucuronosyltransfrease (UGT), respectively (19,20,42). Considering some structural modification Table I.…”

“…Indeed, these polyphenols can express antiproliferative, cytotoxic, proapoptotic, antiinvasive, antimetastatic, antiangiogenic and antiinflammatory properties in different cancer cell lines or animal models (17). However, it is well known that in the human body, flavonoids undergo an extensive metabolism and as a result of this conversion only different metabolic conjugates enter the circulatory system and can reach target malignant tissue (18,19). Differently from parent flavonoids, current knowledge about the possible anticancer action of their metabolites is still rather limited making the prediction of bioactive behavior of flavonoids in the human body complicated.…”