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Monocarboxylate transporter 6 (MCT6; SLC16A5) has been recognized for its role as a xenobiotic transporter, with characterized substrates probenecid, bumetanide, and nateglinide. To date, the impact of commonly ingested dietary compounds on MCT6 function has not been investigated, and therefore, the objective of this study was to evaluate a variety of flavonoids for their potential MCT6-specific interactions. Flavonoids are a large group of polyphenolic phytochemicals found in commonly consumed plant-based products that have been recognized for their dietary health benefits. The uptake of bumetanide in human MCT6 gene-transfected Xenopus laevis oocytes was significantly decreased in the presence of a variety of flavonoids (e.g., quercetin, luteolin, phloretin, and morin), but was not significantly affected by flavonoid glycosides (e.g., naringin, rutin, phlorizin). The IC50 values of quercetin, phloretin, and morin were determined to be 25.3 ± 3.36, 17.3 ± 2.37, and 33.1 ± 3.29 μM, respectively. The mechanism of inhibition of phloretin was reversible and competitive, with a Ki value of 22.8 μM. Furthermore, typical MCT substrates were also investigated for their potential interactions with MCT6. Substrates of MCTs 1, 2, 4, 8, and 10 did not cause any significant decrease in MCT6-mediated bumetanide uptake, suggesting that MCT6 has distinct compound selectivity. In summary, these results suggest that dietary aglycon flavonoids may significantly alter the pharmacokinetics and pharmacodynamics of bumetanide and other MCT6-specific substrates, and may represent potential substrates for MCT6.
An,
Flavonoids are inhibitors of human organic anion transporter 1 (OAT1)-mediated transport.
2014, Pubmed
An,
Flavonoids are inhibitors of human organic anion transporter 1 (OAT1)-mediated transport.
2014,
Pubmed Bansal,
Emerging significance of flavonoids as P-glycoprotein inhibitors in cancer chemotherapy.
2009,
Pubmed Chun,
Estimated dietary flavonoid intake and major food sources of U.S. adults.
2007,
Pubmed Gill,
Expression and membrane localization of MCT isoforms along the length of the human intestine.
2005,
Pubmed Halestrap,
The monocarboxylate transporter family--role and regulation.
2012,
Pubmed Jiang,
Mutual interactions between flavonoids and enzymatic and transporter elements responsible for flavonoid disposition via phase II metabolic pathways.
2012,
Pubmed Jones,
Monocarboxylate Transporters: Therapeutic Targets and Prognostic Factors in Disease.
2016,
Pubmed Kawser Hossain,
Molecular Mechanisms of the Anti-Obesity and Anti-Diabetic Properties of Flavonoids.
2016,
Pubmed Kohyama,
Characterization of monocarboxylate transporter 6: expression in human intestine and transport of the antidiabetic drug nateglinide.
2013,
Pubmed
,
Xenbase Kühnau,
The flavonoids. A class of semi-essential food components: their role in human nutrition.
1976,
Pubmed Kwon,
Inhibition of the intestinal glucose transporter GLUT2 by flavonoids.
2007,
Pubmed
,
Xenbase Moon,
Dietary flavonoids: effects on xenobiotic and carcinogen metabolism.
2006,
Pubmed Morris,
Flavonoid-drug interactions: effects of flavonoids on ABC transporters.
2006,
Pubmed Murakami,
Functional characterization of human monocarboxylate transporter 6 (SLC16A5).
2005,
Pubmed
,
Xenbase Musa-Aziz,
Using fluorometry and ion-sensitive microelectrodes to study the functional expression of heterologously-expressed ion channels and transporters in Xenopus oocytes.
2010,
Pubmed
,
Xenbase Nakamura,
Dihydrochalcones: evaluation as novel radical scavenging antioxidants.
2003,
Pubmed Nigam,
The organic anion transporter (OAT) family: a systems biology perspective.
2015,
Pubmed Peng,
Flavonoid structure affects the inhibition of lipid peroxidation in Caco-2 intestinal cells at physiological concentrations.
2003,
Pubmed Rezk,
The antioxidant activity of phloretin: the disclosure of a new antioxidant pharmacophore in flavonoids.
2002,
Pubmed Scalbert,
Dietary intake and bioavailability of polyphenols.
2000,
Pubmed Shim,
Inhibition effect of flavonoids on monocarboxylate transporter 1 (MCT1) in Caco-2 cells.
2007,
Pubmed Walgren,
Cellular uptake of dietary flavonoid quercetin 4'-beta-glucoside by sodium-dependent glucose transporter SGLT1.
2000,
Pubmed Wang,
Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo.
2007,
Pubmed Wang,
Flavonoids as a novel class of human organic anion-transporting polypeptide OATP1B1 (OATP-C) modulators.
2005,
Pubmed Wong,
Flavonoid conjugates interact with organic anion transporters (OATs) and attenuate cytotoxicity of adefovir mediated by organic anion transporter 1 (OAT1/SLC22A6).
2011,
Pubmed Wu,
Multispecific drug transporter Slc22a8 (Oat3) regulates multiple metabolic and signaling pathways.
2013,
Pubmed Zhang,
Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport.
2004,
Pubmed Zheng,
[Effects of the flavonoids on cytochrome P-450 CYP1, 2E1, 3A4 and 19].
2007,
Pubmed
