The 2-aminoethyl diphenylborinate-based fluorescent method identifies quercetin and luteolin metabolites as substrates of Organic anion transporting polypeptides, OATP1B1 and OATP2B1

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F24%3A00598215" target="_blank" >RIV/61388971:_____/24:00598215 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0928098724000514?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0928098724000514?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejps.2024.106740" target="_blank" >10.1016/j.ejps.2024.106740</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The 2-aminoethyl diphenylborinate-based fluorescent method identifies quercetin and luteolin metabolites as substrates of Organic anion transporting polypeptides, OATP1B1 and OATP2B1

Popis výsledku v původním jazyce

Organic anion transporting polypeptides (OATPs), OATP1B1 and OATP2B1 are membrane proteins mediating the cellular uptake of chemically diverse organic compounds. OATP1B1 is exclusively expressed in hepatocytes and plays a key role in hepatic detoxification. The ubiquitously expressed OATP2B1 promotes the intestinal absorption of orally administered drugs. Flavonoids are widely found in foods and beverages, and many of them can inhibit OATP function, resulting in fooddrug interactions. In our previous work, we have shown that not only luteolin (LUT) and quercetin (Q), but also some of their metabolites can inhibit OATP1B1 and OATP2B1 activity. However, data about the potential direct transport of these flavonoids by OATPs have been incomplete. Hence, in the current study, we developed a simple, fluorescencebased method for the measurement of intracellular flavonoid levels. The method applies a cellpermeable small molecule (2-aminoethyl diphenylborinate, 2APB), that, upon forming a complex with flavonoids, results in their fluorescence enhancement. This way the direct uptake of LUT and Q, and also their metabolites ' could be investigated both by confocal microscopy and in a fluorescence plate reader in living cells. With this approach we identified quercetin-3 ' Osulfate, luteolin-3 ' O glucuronide, luteolin-7- Oglucuronide and luteolin-3 ' Osulfate as substrates of both OATP1B1 and OATP2B1. Our results highlight that OATP1B1 and OATP2B1 can be key participants in the transmembrane movement of LUT and Q conjugates with otherwise low cell permeability. In addition, the novel method developed in this study can be a good completion to existing fluorescencebased assays to investigate OATP function.

Název v anglickém jazyce

The 2-aminoethyl diphenylborinate-based fluorescent method identifies quercetin and luteolin metabolites as substrates of Organic anion transporting polypeptides, OATP1B1 and OATP2B1

Popis výsledku anglicky

Organic anion transporting polypeptides (OATPs), OATP1B1 and OATP2B1 are membrane proteins mediating the cellular uptake of chemically diverse organic compounds. OATP1B1 is exclusively expressed in hepatocytes and plays a key role in hepatic detoxification. The ubiquitously expressed OATP2B1 promotes the intestinal absorption of orally administered drugs. Flavonoids are widely found in foods and beverages, and many of them can inhibit OATP function, resulting in fooddrug interactions. In our previous work, we have shown that not only luteolin (LUT) and quercetin (Q), but also some of their metabolites can inhibit OATP1B1 and OATP2B1 activity. However, data about the potential direct transport of these flavonoids by OATPs have been incomplete. Hence, in the current study, we developed a simple, fluorescencebased method for the measurement of intracellular flavonoid levels. The method applies a cellpermeable small molecule (2-aminoethyl diphenylborinate, 2APB), that, upon forming a complex with flavonoids, results in their fluorescence enhancement. This way the direct uptake of LUT and Q, and also their metabolites ' could be investigated both by confocal microscopy and in a fluorescence plate reader in living cells. With this approach we identified quercetin-3 ' Osulfate, luteolin-3 ' O glucuronide, luteolin-7- Oglucuronide and luteolin-3 ' Osulfate as substrates of both OATP1B1 and OATP2B1. Our results highlight that OATP1B1 and OATP2B1 can be key participants in the transmembrane movement of LUT and Q conjugates with otherwise low cell permeability. In addition, the novel method developed in this study can be a good completion to existing fluorescencebased assays to investigate OATP function.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/GA23-04654S" target="_blank" >GA23-04654S: Chemoenzymatická příprava a biologická aktivita metabolitů polyfenolových sloučenin z potravy</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Pharmaceutical Sciences

ISSN

0928-0987

e-ISSN

1879-0720

Svazek periodika

196

Číslo periodika v rámci svazku

1 May 2024

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

10

Strana od-do

106740

Kód UT WoS článku

001222287500001

EID výsledku v databázi Scopus

2-s2.0-85187560809