Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1

Mandery, Kathrin; Bujok, Krystyna; Schmidt, Ingrid; Keiser, Markus; Siegmund, Werner; Balk, Bettina; König, Jörg; Fromm, Martin F.; Glaeser, Hartmut

doi:10.1016/j.bcp.2010.08.008

Cited by 121 publications

(74 citation statements)

References 34 publications

(56 reference statements)

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“…Of this, about 13.8 mg/d is in the form of quercetin-type flavonols (Cao et al, 2010). Several studies showed that quercetin had an inhibitory effect on OATP2B1's function (Mandery et al, 2010;Satoh et al, 2005;Shirasaka et al, 2013a). Our results were consistent with these reports (Figures 2 and 3, and Table 2).…”

Section: Discussionsupporting

confidence: 91%

“…Inhibition or stimulation of OATP2B1's function by drugs or foods could alter the pharmacokinetics of OATP2B1 substrates and potentially lead to adverse effects. Quite a few interactions between OATP2B1 and natural products have been reported in the literature (Fuchikami et al, 2006;Imanaga et al, 2011;Kock et al, 2013;Li et al, 2014;Mandery et al, 2010;Satoh et al, 2005;Shirasaka et al, 2013a,b;Tapaninen et al, 2010Tapaninen et al, , 2011Roth et al, 2011), suggesting that OATP2B1 could interact with a wide range of natural products. To identify more OATP2B1 modulators from natural products and to avoid potential adverse drug-drug and drug-food interactions, in this work the effects of 27 natural compounds and extracts on the function of OATP2B1 have been investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Roth et al (2011) reported that green tea catechins epicatechin gallate and epigallocatechin gallate significantly inhibited OATP2B1-mediated E3S uptake. Several flavonoids, silymarin flavonolignans, and antidiabetic drugs have also been reported to inhibit OATP2B1 in vitro (Bachmakov et al, 2008;Klatt et al, 2013;Kock et al, 2013;Li et al, 2014;Mandery et al, 2010). These reports demonstrated that OATP2B1 could interact with a wide range of natural products.…”

Section: Introductionmentioning

confidence: 92%

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Identification of natural products as modulators of OATP2B1 using LC-MS/MS to quantify OATP-mediated uptake

Wen

Shi

Bian

et al. 2015

Pharmaceutical Biology

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Context: Organic anion-transporting polypeptide 2B1 (OATP2B1) which is highly expressed in enterocytes and hepatocytes could be a key determinant for the intestinal absorption and hepatic uptake of its substrate drugs. Natural products are commonly used in traditional Chinese medicine, foods, and beverages. Objective: The objective of this study is to determine the OATP2B1-mediated drug interactions that could occur between natural products and OATP2B1 substrate drugs. Materials and methods: Human OATP2B1 was transiently expressed in human embryonic kidney (HEK293) cells and characterized by immunofluorescence, Western blot, and uptake assay. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for detecting OATP2B1 substrates estrone-3-sulfate (E3S) and three statins had been developed and were employed to investigate the effects of 27 frequently used natural products on the function of OATP2B1. Uptake of 5 lM E3S and 1 lM statins in the absence or presence of natural products was measured at 37 C for 2 min with empty vector-and OATP2B1-transfected HEK293 cells. The IC 50 values of inhibitors for OATP2B1-mediated 5 lM E3S uptake were determined. Results: Our results showed that mulberrin, scutellarin, quercetin, and glycyrrhetinic acid were strong inhibitors of OATP2B1-mediate E3S uptake with IC 50 values being 1.8, 2.0, 7.5, and 13.0 lM, which were comparable with their plasma concentrations in clinical trials. They also inhibited OATP-mediated uptake of atorvastatin, fluvastatin, and rosuvastatin. These results indicated that clinically relevant drug interactions could occur between these natural compounds and OATP2B1 substrate drugs. Discussion and conclusion: The information obtained from this study might be helpful to predict and to avoid potential OATP2B1-mediated drug interactions.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

See 1 more Smart Citation

Identification of natural products as modulators of OATP2B1 using LC-MS/MS to quantify OATP-mediated uptake

Wen

Shi

Bian

et al. 2015

Pharmaceutical Biology

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“…Rosuvastatin has a high affinity for OATP transporters, as its K m was determined to be 2.6, 4.0, 9.8, and 2.4 mM for OATP1A2, OATP1B1, OATP1B3, and OATP2B1, respectively (Ho et al, 2006). Finally, OATP1A2 is inhibited by various flavonoids, such as naringin, apigenin, kaempferol, quercetin, and several flavonoids found in green tea Mandery et al, 2010;Roth et al, 2011;Misaka et al, 2014). Flavonoids are found in vegetables, fruits, and plants; thus, pharmacokinetic studies using flavonoids focused on intestinal interactions.…”

Section: Introductionmentioning

confidence: 99%

Effects of β-Blockers and Tricyclic Antidepressants on the Activity of Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2)

Michaud

Moya

et al. 2015

J Pharmacol Exp Ther

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The organic anion transporting polypeptide 1A2 (OATP1A2), a membrane drug transporter expressed on important organs (such as the brain, kidney, and intestine) may be a key element in the disposition of drugs. Previous studies demonstrated that it could transport a broad spectrum of substrates, including endogenous molecules and clinically relevant drugs, such as several b-blockers and 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors. The primary objective of this study was to investigate OATP1A2 transport activity using rosuvastatin as a probe substrate and evaluate competitive inhibition of its transport by b-blockers. Rosuvastatin transport was saturable, with a K m of 60.2 mM. With the exception of carvedilol (IC 50 of 3.2 mM), all of the other b-blockers that were evaluated had a small or insignificant effect on OATP1A2-mediated uptake of rosuvastatin. Carvedilol differs from the other b-blockers by the tricyclic moiety in its chemical structure. As a secondary objective, the transport of a series of tricyclic compounds by OATP1A2 and their potential for rosuvastatin transport inhibition were evaluated. Tricyclic compounds were not OATP1A2 substrates. On the other hand, tricyclic compounds with a short aliphatic amine chain inhibited OATP1A2-mediated rosuvastatin transport. Our data suggest that these drugs may modulate the transport of OATP1A2 substrates and may affect drug actions.

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“…HEK-OATP1A2, HEK-OATP1B1, HEK-OATP1B3, and HEK-OATP2B1 cells and the respective vector-transfected control cells (HEK-VC cells) were established as described previously (Leonhardt et al, 2010;Mandery et al, 2010). For competition assays, the cells were seeded in 24-well plates (BD Biosciences, Heidelberg, Germany) in full growth medium (minimal essential medium supplemented with 10% fetal bovine serum, 2 mM L-glutamine, and 2 mM nonessential amino acids; PAA, Coelbe, Germany) for 3 days, at an initial density of 200,000 cells per well.…”

Section: Methodsmentioning

confidence: 99%

Clarithromycin Is Absorbed by an Intestinal Uptake Mechanism That Is Sensitive to Major Inhibition by Rifampicin: Results of a Short-Term Drug Interaction Study in Foals

Peters¹,

Eggers²,

Oswald³

et al. 2011

Drug Metab Dispos

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ABSTRACT:Pulmonary penetration of clarithromycin (CLR) in epithelial lining fluid (ELF) and bronchoalveolar lavage cells (BALCs) can be influenced by CYP3A4, by P-glycoprotein, and, according to our hypothesis, by a member of the organic anion-transporting protein (OATP) family, for which rifampicin (RIF) is inhibiting in single doses but inducing after long-term coadministration. To assess the partial inhibitory effect, we measured absorption and pulmonary distribution of CLR after short-term (2.5-day) coadministration of RIF, after which up-regulation is not expected. The drug interaction study was performed with five doses (12-h interval) of CLR (7.5 mg/kg) and RIF (10 mg/kg) in nine healthy foals; horse transporters are very similar in protein sequence and transcriptional regulation to the human analogs. RIF was equally distributed in ELF but reached half the plasma levels in BALCs. The deacetylated metabolite accumulated 1.4-to 6-fold in ELF and 8-to 60-fold in BALCs. CLR did not significantly influence the distribution of RIF. CLR and 14-hydroxyclarithromycin (14OH-CLR) accumulated approximately

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Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1

Cited by 121 publications

References 34 publications

Identification of natural products as modulators of OATP2B1 using LC-MS/MS to quantify OATP-mediated uptake

Identification of natural products as modulators of OATP2B1 using LC-MS/MS to quantify OATP-mediated uptake

Effects of β-Blockers and Tricyclic Antidepressants on the Activity of Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2)

Clarithromycin Is Absorbed by an Intestinal Uptake Mechanism That Is Sensitive to Major Inhibition by Rifampicin: Results of a Short-Term Drug Interaction Study in Foals

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