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Involvement of cytochrome P450 enzymes in metabolism of flavonoid aglycones

Flavonoids are secondary plant products found in vegetables and fruits in everyday diet. This class of compounds is characterized with C6-C3- C6 skeleton i.e. benzopyran ring to which phenyl is bound (Figure 1). Diversity of these compounds comes from hydroxylation and subsequent methylation and glycosylation of hydroxyl groups. Flavonoids have been compounds of interest due to their numerous potential benefits on health mainly antioxidant and cardioprotective. Objective of this study was to screen metabolism of 30 flavonoids using human liver microsomes and recombinant liver cytochrome P450 enzymes. For this purpose, HPLC method coupled with UV detector and MS TOF was developed. This method combined separation power of HPLC and determination of accurate mass of unknown metabolites using MS TOF. Most 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 were confirmed using flavonoid standards. Out of 30 flavonoids 11 have shown metabolism mediated by cytochrome P450 namely 3, 7- dihydroxyflavone, 6-hydroxyflavone, 7- hydroxyflavone, acacetin, apigenin, flavone, galangin, kaempferol, naringenin, sakuranetin and tangeretin. Mostly hydroxylations and demethylations of flavonoid substrates were observed. The most significant enzyme involved in metabolism of analyzed flavonoids was cytochrome P450 1A2 which is in accordance with previously reported data. 7-Hydroxyflavone, acacetin and tangeretin were metabolized by cytochrome P450 2D6. Galangin and 6- hydroxyflavone were metabolized by cytochrome P450 2C19. 7-Hydroxyflavone, sakuranetin and tangeretin were metabolized by cytochrome P450 3A4.

flavonoids, metabolism

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