title: Effect of quercetin on the transport of N-acetyl 5-aminosalicylic acid.
abstract: OBJECTIVE
  The aim of this study was to investigate the transporter-mediated transport of N-acetyl 5-aminosalicylic acid (Ac-5-ASA) and the effect of quercetin on Ac-5-ASA transport.
  
  
  METHODS
  Caco-2 cell monolayers grown in Transwells were used to study the transport of Ac-5-ASA in the absence or presence of quercetin, and apical-to-basolateral and basolateral-to-apical apparent permeability (PappAB and PappBA values, respectively) was determined. The effect of transporter inhibitors, such as MK571, quinidine and mitoxantrone, on the transport of Ac-5-ASA was investigated.
  
  
  RESULTS
  In the absence of transporter mediators, the transport of Ac-5-ASA was much higher in the basolateral-to-apical direction than in the opposite direction. The PappBA/PappAB ratio of Ac-5-ASA was 4.89. Quercetin inhibited the apical efflux of Ac-5-ASA and decreased the PappBA/PappAB ratio to 1.05. Of the transporter inhibitors, MK571 decreased the PappBA/PappAB ratio to 1.07; however, neither quinidine nor mitoxantrone had an effect on Ac-5-ASA transport.
  
  
  CONCLUSIONS
  Ac-5-ASA was excreted by multidrug resistance-associated protein 2 from Caco-2 cells, and its transport was inhibited by quercetin. Our findings suggest that dose levels of sulfasalazine or 5-aminosalicylic acid can be decreased by coadministration of quercetin, leading to improved pharmaceutical care for inflammatory bowel diseases.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kamishikiryo
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Matsumura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Takamori
authors.forename: Narumi
authors.initials: N
authors.lastname: Sugihara
mesh_terms: D000636:Aminosalicylic Acids / Q000493:pharmacokinetics*; D001692:Biological Transport; D018938:Caco-2 Cells; D004347:Drug Interactions; D006801:Humans; D008942:Mitoxantrone / Q000494:pharmacology; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology
chemical_list: D000636:Aminosalicylic Acids; D008942:Mitoxantrone; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011422:Propionates; D011794:Quercetin; D011802:Quinidine; D011804:Quinolines; C059141:verlukast; C028836:N-acetyl-5-aminosalicylic acid