<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Biological effects of flavonoids have been extensively studied in the last 80 years. As flavonoids represent a rather large group of compounds, data on metabolic biotransformations of these compounds is relatively limited to those well studied. The objective of this study was to screen the metabolism of 30 selected flavonoid aglycons mediated by the most relevant metabolic enzymes, human liver cytochromes P450. For this purpose, <italic>in vitro</italic> experiments with human liver microsomes and recombinant enzymes were conducted. To evaluate flavonoid’s metabolism and structure of the products, high-performance liquid chromatography coupled with high-resolution mass spectrometry was used. Out of 30 flavonoids, 15 were susceptible to oxidative metabolism mediated by cytochromes P450. Dominant reactions were aromatic hydroxylation and <italic>O</italic>-demethylation, or a combination of these reactions. The dominant enzyme responsible for the observed metabolic reactions is CYP1A2, whereas other human liver cytochromes P450, namely, CYP2C19, CYP2D6, CYP2E1 and CYP3A4, contribute to flavonoid metabolism to a lesser degree. These results, to some extent, contribute to the understanding of the metabolism of constituents found in antioxidant dietary supplements and their possible interactions with other xenobiotics, <italic>i.e</italic>., medicinal products.</p></abstract>

Biological effects of flavonoids have been extensively studied in the last 80 years. As flavonoids represent a rather large group of compounds, data on metabolic biotransformations of these compounds is relatively limited to those well studied. The objective of this study was to screen the metabolism of 30 selected flavonoid aglycons mediated by the most relevant metabolic enzymes, human liver cytochromes P450. For this purpose, in vitro experiments with human liver microsomes and recombinant enzymes were conducted. To evaluate flavonoid’s metabolism and structure of the products, high-performance liquid chromatography coupled with high-resolution mass spectrometry was used. Out of 30 flavonoids, 15 were susceptible to oxidative metabolism mediated by cytochromes P450. Dominant reactions were aromatic hydroxylation and O-demethylation, or a combination of these reactions. The dominant enzyme responsible for the observed metabolic reactions is CYP1A2, whereas other human liver cytochromes P450, namely, CYP2C19, CYP2D6, CYP2E1 and CYP3A4, contribute to flavonoid metabolism to a lesser degree. These results, to some extent, contribute to the understanding of the metabolism of constituents found in antioxidant dietary supplements and their possible interactions with other xenobiotics, i.e., medicinal products.

Screening of flavonoid aglycons’ metabolism mediated by the human liver cytochromes P450

Faculty of Pharmacy and Biochemistry Department of Medicinal Chemistry

Faculty of Pharmacy and Biochemistry Department of Pharmaceutical Botany

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Biological effects of flavonoids have been extensively studied in the last 80 years. As flavonoids represent a rather large group of compounds, data on...

Screening of flavonoid aglycons’ metabolism mediated by the human liver cytochromes P450

Published Online: Oct 21, 2019

Page range: 541 - 562

Accepted: Jul 23, 2019

DOI: https://doi.org/10.2478/acph-2019-0039

Keywords
flavonoids, human liver cytochromes P450, metabolism, HPLC, MS

© 2019 Goran Benković et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Screening of flavonoid aglycons’ metabolism mediated by the human liver cytochromes P450

Published Online: Oct 21, 2019

Page range: 541 - 562

Accepted: Jul 23, 2019

DOI: https://doi.org/10.2478/acph-2019-0039

Keywordsflavonoids, human liver cytochromes P450, metabolism, HPLC, MS

© 2019 Goran Benković et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
flavonoids, human liver cytochromes P450, metabolism, HPLC, MS