Inhibition of hepatic uptake transporters by flavonoids

Mandery, Kathrin; Balk, Bettina; Bujok, Krystyna; Schmidt, Ingrid; Fromm, Martin F.; Glaeser, Hartmut

doi:10.1016/j.ejps.2012.02.014

Cited by 61 publications

(41 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Kaempferol was already characterized as a competitive inhibitor of several human OATPs (Mandery et al 2010a(Mandery et al , 2012. In the present study, kaempferol was not transported Fig.…”

Section: Discussioncontrasting

confidence: 58%

“…Flavonoids like quercetin and kaempferol are constituents of fruits, vegetables, beverages (red wine), and herbal drugs (Ginkgo biloba formulations) (Hertog et al 1992(Hertog et al , 1993b. Mandery and colleagues previously demonstrated that the flavonoids apigenin, kaempferol, and quercetin inhibit the drug uptake transporters OATP1A2, OATP1B1, OATP1B3, and OATP2B1 (Mandery et al 2010a(Mandery et al , 2012.…”

Section: Discussionmentioning

confidence: 97%

“…The used human embryonic kidney (HEK) 293 cell lines overexpressing certain transporters have previously been characterized regarding expression and/or function (Seithel et al 2007;Bachmakov et al 2008;Kraft et al 2010;Mandery et al 2010bMandery et al , 2012Kindla 2011;Kindla et al 2011;König et al 2011;Banerjee et al 2012;Münch et al 2012Münch et al , 2013. In brief, HEK293 cells, stably expressing organic OATP1A2 (HEK293-OATP1A2) and the respective control cells (HEK293-VC, cells stably transfected with the respective empty expression vector: pQCXIN), were cultured in minimum essential medium containing 10 % heatinactivated fetal bovine serum, 0.1 mM non-essential amino acids, 800 μg/ml geneticin, 100 U/ml penicillin, and 100 mg/ml streptomycin at 37°C and 5 % CO 2 (Mandery et al 2010a).…”

Section: Cell Culturementioning

confidence: 98%

“…HEK293-OATP1B1 (Seithel et al 2007), HEK293-OATP2A1 (Mandery et al 2010b), HEK293-OATP2B1 cells (Bachmakov et al 2008;Kraft et al 2010), HEK293-OATP3A1 (Kindla 2011;Kindla et al 2011;Banerjee et al 2012), HEK293-OATP4A1 Banerjee et al 2012), HEK293-OATP5A1 (Kindla et al 2011), and the respective control [HEK293-VC, empty vector: pcDNA3.1(+)-G418] were cultured in minimum essential medium containing 10 % heat-inactivated fetal bovine serum, 800 μg/ml geneticin, 100 U/ml penicillin, and 100 mg/ml streptomycin at 37°C and 5 % CO 2 . HEK293-OATP1B3 cells (Seithel et al 2007) and HEK293-OCT1 (Mandery et al 2012;Münch et al 2012Münch et al , 2013 and the respective control cells [HEK293-VC, empty vector: pcDNA3.1(-)-Hygromycin] were cultured in minimum essential medium containing 10 % heat-inactivated fetal bovine serum, 250 μg/ml hygromycin, 100 U/ml penicillin, and 100 mg/ml streptomycin at 37°C and 5 % CO 2 . The cells were routinely subcultured by trypsinization using trypsin (0.05 %)-EDTA (0.02 %) solution.…”

Section: Cell Culturementioning

confidence: 99%

“…Therefore, we investigated the contribution of several SLC transporters on the cellular accumulation of quercetin and kaempferol. In addition to SLC transporters, which have been shown to be inhibited by kaempferol and quercetin (Mandery et al 2010a(Mandery et al , 2012, we also investigated further SLC transporters, which are currently not well functionally characterized (e.g., OATP3A1, OATP4A1, OATP5A1) in order to gain more insights into the possible functional relevance of such transporters.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Organic anion transporting polypeptides and organic cation transporter 1 contribute to the cellular uptake of the flavonoid quercetin

Glaeser

Bujok

Schmidt

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

Self Cite

View full text Add to dashboard Cite

Flavonoids such as quercetin and kaempferol mediate several health protective effects, e.g., anticancer effects. They are inhibitors of organic anion transporting polypeptides (OATP) and organic cation transporters (e.g., OCT2). However, little is known whether such transporters contribute to the cellular uptake of flavonoids. Therefore, we investigated the cellular uptake of kaempferol and quercetin using HEK293 cell lines stably expressing different human OATPs or OCT1. Kaempferol was not a substrate of any of the investigated transporters (OATP1A2, OATP1B1, OATP1B3, OATP2A1, OATP2B1, OATP3A1, OATP4A1, OATP5A1, and OCT1). Quercetin showed a significantly higher uptake into the HEK293-OATP1A2, HEK293-OATP2A1, HEK293-OATP2B1, and HEK293-OCT1 cells compared to control cells. The OATP1A2-, OATP2B1-, and OCT1-mediated quercetin uptake was inhibited by known inhibitors such as naringin, cyclosporin A, and quinidine, respectively. The cellular accumulation of quercetin into HEK293-OATP2A1 cells was not inhibited by prostaglandin E2 and diclofenac. The ionophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) reduced the net uptake of quercetin by increasing the uptake in the HEK293-control cells and causing no significant change in the HEK293-OATP2B1 cells indicating that quercetin follows the FCCP-driven proton flux through the plasma membrane. In addition to passive diffusion, the SLC transporters OATP1A2, OATP2B1, and OCT1 contribute to cellular accumulation of quercetin.

show abstract

“…Kaempferol was already characterized as a competitive inhibitor of several human OATPs (Mandery et al 2010a(Mandery et al , 2012. In the present study, kaempferol was not transported Fig.…”

Section: Discussioncontrasting

confidence: 58%

Section: Discussionmentioning

confidence: 97%

Section: Cell Culturementioning

confidence: 98%

Section: Cell Culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Organic anion transporting polypeptides and organic cation transporter 1 contribute to the cellular uptake of the flavonoid quercetin

Glaeser

Bujok

Schmidt

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

Self Cite

View full text Add to dashboard Cite

show abstract

Physiological, Biochemical, and Chemical Barriers to Oral Drug Delivery

2016

View full text Add to dashboard Cite

In Vitro and In Silico Studies to Explore Structural Features of Flavonoids for Aldehyde Oxidase Inhibition

Hamzeh‐Mivehroud

Rahmani

Feizi

et al. 2014

Archiv der Pharmazie

View full text Add to dashboard Cite

Aldehyde oxidase (AO), an important enzyme in the biotransformation of drugs and xenobiotics, is inhibited by flavonoids. This enzyme can metabolize both aldehydes and N-heterocycles. In this work, a set of 15 flavonoids was assessed for inhibitory activity on the AO oxidation of vanillin as an aldehyde substrate. Spectrophotometrically determined IC50 values showed that myricetin, quercetin, and epicatechin were the most potent inhibitors. The results also revealed that the inhibition of vanillin oxidation by flavonoids was stronger than that of phenanthridine oxidation (an N-heterocyclic substrate) as reported previously. In order to investigate the important structural features responsible for the inhibitory effects of the studied flavonoids, a quantitative structure-activity relationship (QSAR) analysis was performed. This study showed that the size of the flavonoids was the most important factor inversely affecting their potencies. The QSAR model can be used more broadly to predict the AO inhibitory activity of flavonoid-like structures for application in food-drug and drug-drug interaction studies.

show abstract

Inhibition of hepatic uptake transporters by flavonoids

Cited by 61 publications

References 37 publications

Organic anion transporting polypeptides and organic cation transporter 1 contribute to the cellular uptake of the flavonoid quercetin

Organic anion transporting polypeptides and organic cation transporter 1 contribute to the cellular uptake of the flavonoid quercetin

Physiological, Biochemical, and Chemical Barriers to Oral Drug Delivery

In Vitro and In Silico Studies to Explore Structural Features of Flavonoids for Aldehyde Oxidase Inhibition

Contact Info

Product

Resources

About