Honey flavonoids inhibit hOATP2B1 and hOATP1A2 transporters and hOATP-mediated rosuvastatin cell uptake in vitro

Abstract

1. Some flavonoids contained in the common diet have been shown to interact with important membrane uptake transporters, including organic anion transporting polypeptides (OATPs). OATP2B1 and OATP1A2 expressed in the apical membrane of human enterocytes may significantly contribute to the intestinal absorption of drugs, e.g. statins. This study is aimed at an evaluation of the inhibitory potency of selected food honey flavonoids (namely galangin, myricetin, pinocembrin, pinobanksin, chrysin and fisetin) toward hOATP2B1 and hOATP1A2 as well as at examining their effect on the cellular uptake of the known OATP substrate rosuvastatin.

2. Cell lines overexpressing the hOATP2B1 or hOATP1A2 transporter were employed as in vitro model to determine the inhibitory potency of the flavonoids toward the OATPs.

3. Chrysin, galangin and pinocembrin were found to inhibit both hOATP2B1 and hOATP1A2 in lower or comparable concentrations as the known flavonoid OATP inhibitor quercetin. Galangin, chrysin and pinocembrin effectively inhibited rosuvastatin uptake by hOATP2B1 with IC₅₀ ∼1–10 μM. The inhibition of the hOATP1A2-mediated transport of rosuvastatin by these flavonoids was weaker.

4. The found data indicate that several of the tested natural compounds could potentially affect drug cellular uptake by hOATP2B1 and/or hOATP1A2 at relative low concentrations, a finding which suggests their potential for food–drug interactions.

• Drug transporters
• food–drug interactions
• intestinal absorption
• organic anion-transporting polypeptides
• statins

Acknowledgments

This work was supported by the Grant Agency of Charles University [grant 30216/C/2016]; Charles University [grants SVV 260 414, PRVOUK P40]; and the Grant Agency of Czech Republic [grant P303/12/G163].

We thank Dr. Rudolf Andrýs for help and advices with Western blot analysis.

Declaration of interest

The authors report no conflicts of interest.