The 2-aminoethyl diphenylborinate-based fluorescent method identifies quercetin and luteolin metabolites as substrates of Organic anion transporting polypeptides, OATP1B1 and OATP2B1
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
The 2-aminoethyl diphenylborinate-based fluorescent method identifies quercetin and luteolin metabolites as substrates of Organic anion transporting polypeptides, OATP1B1 and OATP2B1
Original language description
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.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/GA23-04654S" target="_blank" >GA23-04654S: Chemoenzymatic preparation and biological activity of metabolites of food polyphenols</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
European Journal of Pharmaceutical Sciences
ISSN
0928-0987
e-ISSN
1879-0720
Volume of the periodical
196
Issue of the periodical within the volume
1 May 2024
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
10
Pages from-to
106740
UT code for WoS article
001222287500001
EID of the result in the Scopus database
2-s2.0-85187560809