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

Membrane organic anion-transporting polypeptides (OATPs) are responsible for the drug transmembrane transport within the human body. The function of OATP2B1 transporter can be inhibited by various natural compounds. Despite increased research interest in soya as a part of human diet, the effect of its active components to interact with hOATP2B1 has not been elucidated in a complex extent. This in vitro study examined the inhibitory effect of main soy isoflavones (daidzin, daidzein, genistin, genistein, glycitin, glycitein, biochanin A, formononetin) and their metabolites formed in vivo (S-equol, O-desmethylangolensin) towards human OATP2B1 transporter. MDCKII cells overexpressing hOATP2B1 were employed to determine quantitative inhibitory parameters of the tested compounds and to analyze mechanism/s of the inhibitory interaction. The study showed that aglycones of soy isoflavones and the main biologically active metabolite S-equol were able to significantly inhibit hOATP2B1-mediated transport. The Ki values for most of aglycones range from 1 to 20 μM. In contrast, glucosides did not exhibit significant inhibitory effect. The kinetic analysis did not indicate a uniform type of inhibition towards the hOATP2B1 although predominant mechanism of inhibition seemed to be competitive. These findings may suggest that tested soy isoflavones and their metabolites might affect transport of xenobiotics including drugs across tissue barriers via hOATP2B1.

• Klíčová slova
• Drug transporter, Flavonoids, OATP, SLCO, Soy isoflavones,
• MeSH
• buňky MDCK MeSH
• Glycine max * MeSH
• isoflavony farmakologie   MeSH
• kinetika MeSH
• přenašeče organických aniontů antagonisté a inhibitory   genetika   metabolismus   MeSH
• psi MeSH
• transfekce MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• isoflavony MeSH
• přenašeče organických aniontů MeSH
• SLCO2B1 protein, human MeSH Prohlížeč