Myricetin (MYR) and ampelopsin (AMP, or dihydromyricetin) are flavonoid aglycones found in certain plants and dietary supplements. During the presystemic biotransformation of flavonoids, mainly sulfate and glucuronide derivatives are produced, which are the dominant metabolites in the circulation. In this study, we tested the interactions of MYR, myricetin-3'-O-sulfate (M3'S), AMP, and ampelopsin-4'-O-sulfate (A4'S) with human serum albumin (HSA), cytochrome P450 enzymes (CYPs), and organic anion-transporting polypeptides (OATPs) using in vitro models, including the recently developed method for measuring flavonoid levels in living cells. M3'S and MYR bound to albumin with high affinity, and they showed moderate displacing effects versus the Site I marker warfarin. MYR, M3'S, AMP, and A4'S exerted no or only minor inhibitory effects on CYP2C9, CYP2C19, and CYP3A4 enzymes. M3'S and MYR caused considerable inhibitory actions on OATP1B1 at low micromolar concentrations (IC50 = 1.7 and 6.4 μM, respectively), while even their nanomolar levels resulted in strong inhibitory effects on OATP2B1 (IC50 = 0.3 and 0.4 μM, respectively). In addition, M3'S proved to be a substrate of OATP1B1 and OATP2B1. These results suggest that MYR-containing dietary supplements may affect the OATP-mediated transport of certain drugs, and OATPs are involved in the tissue uptake of M3'S.

• Klíčová slova
• CYP enzymes, OATP transporters, ampelopsin, human serum albumin, myricetin,
• MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• cytochrom P450 CYP2C9 metabolismus   MeSH
• flavonoidy * farmakologie   MeSH
• flavonoly farmakologie   MeSH
• lidé MeSH
• polypeptid C přenášející organické anionty * metabolismus   MeSH
• přenašeče organických aniontů * metabolismus   MeSH
• sérový albumin metabolismus   MeSH
• sírany metabolismus   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ampelopsin MeSH Prohlížeč
• CYP3A4 protein, human MeSH Prohlížeč
• cytochrom P-450 CYP3A MeSH
• cytochrom P450 CYP2C9 MeSH
• dihydromyricetin MeSH Prohlížeč
• flavonoidy * MeSH
• flavonoly MeSH
• myricetin MeSH Prohlížeč
• polypeptid C přenášející organické anionty * MeSH
• přenašeče organických aniontů * MeSH
• sérový albumin MeSH
• sírany MeSH
• SLCO1B1 protein, human MeSH Prohlížeč
• SLCO2B1 protein, human MeSH Prohlížeč
• systém (enzymů) cytochromů P-450 MeSH

Cytochrome P450 (CYP) is a major group of enzymes, which conduct Phase I metabolism. Among commonly used animal models, the pig has been suggested as the most suitable model for investigating drug metabolism in human beings. Moreover, porcine CYP2A19 and CYP2E1 are responsible for the biotransformation of both endogenous and exogenous compounds such as 3-methylindole (skatole), sex hormones and food compounds. However, little is known about the regulation of porcine CYP2A19 and CYP2E1. In this MiniReview, we summarise the current knowledge about the regulation of porcine CYP2A19 and CYP2E1 by environmental, biological and dietary factors. Finally, we reflect on the need for further research, to clarify the interaction between active feed components and the porcine CYP system.

• Klíčová slova
• bioactive compounds, phase I enzymes, pig, skatole,
• MeSH
• biotransformace MeSH
• cytochrom P-450 CYP2E1 genetika   metabolismus   MeSH
• cytochrom P450 CYP2A6 genetika   metabolismus   MeSH
• krmivo pro zvířata * MeSH
• lidé MeSH
• pohlavní steroidní hormony metabolismus   MeSH
• prasata metabolismus   MeSH
• sekvenční homologie MeSH
• skatol metabolismus   MeSH
• xenobiotika metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cytochrom P-450 CYP2E1 MeSH
• cytochrom P450 CYP2A6 MeSH
• pohlavní steroidní hormony MeSH
• skatol MeSH
• xenobiotika MeSH