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Inhibitory Effects of Green Tea and (-)-Epigallocatechin Gallate on Transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-Glycoprotein.

Knop J, Misaka S, Singer K, Hoier E, Müller F, Glaeser H, König J, Fromm MF - PLoS ONE (2015)

Bottom Line: OCT1-, OCT2-, MATE1- and MATE2-K-mediated metformin uptake was significantly reduced in the presence of green tea and EGCG (P < 0.05).Basolateral to apical transport of digoxin was significantly decreased in the presence of green tea and EGCG.Further studies are necessary to investigate the effects of green tea on prototoypical substrates of these transporters in humans, in particular on substrates of hepatic uptake transporters (e.g. statins) as well as on P-glycoprotein substrates.

View Article: PubMed Central - PubMed

Affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

ABSTRACT
Green tea catechins inhibit the function of organic anion transporting polypeptides (OATPs) that mediate the uptake of a diverse group of drugs and endogenous compounds into cells. The present study was aimed at investigating the effect of green tea and its most abundant catechin epigallocatechin gallate (EGCG) on the transport activity of several drug transporters expressed in enterocytes, hepatocytes and renal proximal tubular cells such as OATPs, organic cation transporters (OCTs), multidrug and toxin extrusion proteins (MATEs), and P-glycoprotein (P-gp). Uptake of the typical substrates metformin for OCTs and MATEs and bromosulphophthalein (BSP) and atorvastatin for OATPs was measured in the absence and presence of a commercially available green tea and EGCG. Transcellular transport of digoxin, a typical substrate of P-gp, was measured over 4 hours in the absence and presence of green tea or EGCG in Caco-2 cell monolayers. OCT1-, OCT2-, MATE1- and MATE2-K-mediated metformin uptake was significantly reduced in the presence of green tea and EGCG (P < 0.05). BSP net uptake by OATP1B1 and OATP1B3 was inhibited by green tea [IC50 2.6% (v/v) and 0.39% (v/v), respectively]. Green tea also inhibited OATP1B1- and OATP1B3-mediated atorvastatin net uptake with IC50 values of 1.9% (v/v) and 1.0% (v/v), respectively. Basolateral to apical transport of digoxin was significantly decreased in the presence of green tea and EGCG. These findings indicate that green tea and EGCG inhibit multiple drug transporters in vitro. Further studies are necessary to investigate the effects of green tea on prototoypical substrates of these transporters in humans, in particular on substrates of hepatic uptake transporters (e.g. statins) as well as on P-glycoprotein substrates.

No MeSH data available.


Related in: MedlinePlus

Effect of EGCG on OATP1B1- and OATP1B3-mediated BSP and atorvastatin transport.Data are shown as mean ± S.E.M. *** p< 0.001, ** p<0.01, * p<0.05 vs. VC, + p<0.05, +++ p<0.001 vs. corresponding transport without inhibitor.
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pone.0139370.g004: Effect of EGCG on OATP1B1- and OATP1B3-mediated BSP and atorvastatin transport.Data are shown as mean ± S.E.M. *** p< 0.001, ** p<0.01, * p<0.05 vs. VC, + p<0.05, +++ p<0.001 vs. corresponding transport without inhibitor.

Mentions: The uptake of BSP or atorvastatin was measured in the absence or presence of EGCG [100 μM (Fig 4)]. OATP1B1-mediated uptake of BSP or atorvastatin was 7.7-fold (p<0.001) and 1.3-fold (p<0.01) higher compared to VC cells, respectively. In the presence of 100 μM EGCG the OATP1B1-mediated BSP or atorvastatin uptake was 6.7-fold (p<0.01) and 1.2-fold (p<0.05) higher compared to VC cells. OATP1B1-mediated BSP and atorvastatin net uptake (i.e. uptake into transporter-transfected cells minus uptake into vector control cells) were reduced by EGCG to 64% (n.s.) and 69% (p<0.05), respectively, of net uptake without EGCG.


Inhibitory Effects of Green Tea and (-)-Epigallocatechin Gallate on Transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-Glycoprotein.

Knop J, Misaka S, Singer K, Hoier E, Müller F, Glaeser H, König J, Fromm MF - PLoS ONE (2015)

Effect of EGCG on OATP1B1- and OATP1B3-mediated BSP and atorvastatin transport.Data are shown as mean ± S.E.M. *** p< 0.001, ** p<0.01, * p<0.05 vs. VC, + p<0.05, +++ p<0.001 vs. corresponding transport without inhibitor.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591125&req=5

pone.0139370.g004: Effect of EGCG on OATP1B1- and OATP1B3-mediated BSP and atorvastatin transport.Data are shown as mean ± S.E.M. *** p< 0.001, ** p<0.01, * p<0.05 vs. VC, + p<0.05, +++ p<0.001 vs. corresponding transport without inhibitor.
Mentions: The uptake of BSP or atorvastatin was measured in the absence or presence of EGCG [100 μM (Fig 4)]. OATP1B1-mediated uptake of BSP or atorvastatin was 7.7-fold (p<0.001) and 1.3-fold (p<0.01) higher compared to VC cells, respectively. In the presence of 100 μM EGCG the OATP1B1-mediated BSP or atorvastatin uptake was 6.7-fold (p<0.01) and 1.2-fold (p<0.05) higher compared to VC cells. OATP1B1-mediated BSP and atorvastatin net uptake (i.e. uptake into transporter-transfected cells minus uptake into vector control cells) were reduced by EGCG to 64% (n.s.) and 69% (p<0.05), respectively, of net uptake without EGCG.

Bottom Line: OCT1-, OCT2-, MATE1- and MATE2-K-mediated metformin uptake was significantly reduced in the presence of green tea and EGCG (P < 0.05).Basolateral to apical transport of digoxin was significantly decreased in the presence of green tea and EGCG.Further studies are necessary to investigate the effects of green tea on prototoypical substrates of these transporters in humans, in particular on substrates of hepatic uptake transporters (e.g. statins) as well as on P-glycoprotein substrates.

View Article: PubMed Central - PubMed

Affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

ABSTRACT
Green tea catechins inhibit the function of organic anion transporting polypeptides (OATPs) that mediate the uptake of a diverse group of drugs and endogenous compounds into cells. The present study was aimed at investigating the effect of green tea and its most abundant catechin epigallocatechin gallate (EGCG) on the transport activity of several drug transporters expressed in enterocytes, hepatocytes and renal proximal tubular cells such as OATPs, organic cation transporters (OCTs), multidrug and toxin extrusion proteins (MATEs), and P-glycoprotein (P-gp). Uptake of the typical substrates metformin for OCTs and MATEs and bromosulphophthalein (BSP) and atorvastatin for OATPs was measured in the absence and presence of a commercially available green tea and EGCG. Transcellular transport of digoxin, a typical substrate of P-gp, was measured over 4 hours in the absence and presence of green tea or EGCG in Caco-2 cell monolayers. OCT1-, OCT2-, MATE1- and MATE2-K-mediated metformin uptake was significantly reduced in the presence of green tea and EGCG (P < 0.05). BSP net uptake by OATP1B1 and OATP1B3 was inhibited by green tea [IC50 2.6% (v/v) and 0.39% (v/v), respectively]. Green tea also inhibited OATP1B1- and OATP1B3-mediated atorvastatin net uptake with IC50 values of 1.9% (v/v) and 1.0% (v/v), respectively. Basolateral to apical transport of digoxin was significantly decreased in the presence of green tea and EGCG. These findings indicate that green tea and EGCG inhibit multiple drug transporters in vitro. Further studies are necessary to investigate the effects of green tea on prototoypical substrates of these transporters in humans, in particular on substrates of hepatic uptake transporters (e.g. statins) as well as on P-glycoprotein substrates.

No MeSH data available.


Related in: MedlinePlus