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.
Highlights
It is well recognized that food ingredients can alter pharmacokinetics and effects of concomitantly administered drugs [1,2,3,4]
Metformin uptake was inhibited in a concentration dependent manner in the presence of green tea with IC50 values of 1.4% (v/v) and 7.0% (v/v) for OCT1 and OCT2, respectively (Fig 1 and S1 Fig)
To further analyze the inhibitory potency of green tea on drug transport we analyzed in the present study the effect of green tea and its main catechin epigallocatechin gallate (EGCG) on seven important drug transporters expressed in intestine, liver and kidney
Summary
It is well recognized that food ingredients (e.g. furanocoumarins in grapefruit juice) can alter pharmacokinetics and effects of concomitantly administered drugs [1,2,3,4]. Inhibition of Drug Transporters by Green Tea. Pharma, Boehringer Ingelheim Pharma, SanofiAventis Deutschland and Merck KGaA. M.F.F.’s institution received compensation for commissioned research of his group from Merck KGaA and SanofiAventis Deutschland and for supply for in vitro studies from Gilead. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. The remaining authors declare no conflicts of interest
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
