Inhibitory effects of polyphenols and their colonic metabolites on CYP2D6 enzyme using two different substrates

Biomedicine & Pharmacotherapy

Přemysl Mladěnka¹  Violetta Mohos¹  Rita Csepregi²  Eszter Fliszár-Nyúl²  Miklós Poór³ 

[1] Lab-on-a-Chip Research Group, János Szentágothai Research Centre, Ifjúság útja 20, H-7624, Pécs, Hungary;Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, H-7624, Pécs, Hungary;Lab-on-a-Chip Research Group, János Szentágothai Research Centre, Ifjúság útja 20, H-7624, Pécs, Hungary;

关键词: Cytochrome P450;    CYP2D6;    Polyphenols;    Colonic flavonoid metabolites;    Enzyme inhibition;    Pharmacokinetic interaction;   

DOI  :  

来源: DOAJ

【 摘 要 】

Polyphenolic compounds (including flavonoids, chalcones, phenolic acids, and furanocoumarins) represent a common part of our diet, but are also the active ingredients of several dietary supplements and/or medications. These compounds undergo extensive metabolism by human biotransformation enzymes and the microbial flora of the colon. CYP2D6 enzyme metabolizes approximately 25% of the drugs, some of which has narrow therapeutic window. Therefore, its inhibition can lead to the development of pharmacokinetic interactions and the disruption of drug therapy. In this study, the inhibitory effects of 17 plant-derived compounds and 19 colonic flavonoid metabolites on CYP2D6 were examined, employing two assays with different test substrates. The O-demethylation of dextromethorphan was tested employing CypExpress 2D6 kit coupled to HPLC analysis; while the O-demethylation of another CYP2D6 specific substrate (AMMC) was investigated in a plate reader assay with BioVision Fluorometric CYP2D6 kit. Interestingly, some compounds (e.g., bergamottin) inhibited both dextromethorphan and AMMC demethylation; however, certain substances proved to be inhibitors only in one of the assays applied. Our results demonstrate that some polyphenols and colonic metabolites are inhibitors of CYP2D6-catalyzed reactions. Nevertheless, the inhibitory effects showed strong substrate dependence.

【 授权许可】

Unknown