Cytochromes P450 Involved in Metabolism of Flavonoid Aglycones

Abstract

Flavonoids are secondary plant metabolites to which we are exposed through everyday diet (vegetables, fruits, dietary supplements, herbal drugs). They represent a wide class of compounds that have extensively been studied due to beneficial biological effects. As we have evolutionary been exposed to these compounds, human body has developed mechanisms how to excrete these compounds (metabolism, transporters). Objective of this study was to determine cytochromes P450 involved in metabolism of flavonoid aglycones and characterize generated metabolites. Metabolism of 30 flavonoids was assessed using human liver microsomes and recombinant liver cytochrome P450 enzymes. HPLC method coupled with UV detector and MS TOF was used for detection and quantification. Flavonoids could be separated based on retention time even though there are subtle differences in flavonoid structures. Structures of metabolites were elucidated using accurate mass data, retention time and confirmed using flavonoid standards. Flavonoid aglycones are susceptible to hydroxylation and demethylation reactions. The most significant enzyme involved in metabolism of analyzed flavonoids was cytochrome P450 1A2 which is in accordance with previously reported data. Other enzymes involved in metabolism of flavonoid aglycones were cytochromes P450 2D6, 2C19, and 3A4. As data on pharmacokinetics of flavonoids is limited to few well studied flavonoids, understanding metabolism of flavonoids will improve efforts to obtain flavonoid candidates less susceptible to metabolic elimination.Support or Funding InformationThis work was supported by the Croatian Science Foundation under the project UIP‐2014‐09‐5704 (M.B.).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.