title: Interactions of the active components of Punica granatum (pomegranate) with the essential renal and hepatic human Solute Carrier transporters.
abstract: Abstract Context: Solute carrier transporters (SLCs) are membrane proteins responsible for cellular influx of various substances including many pharmaceutical agents; therefore, they largely impact on drug disposition and elimination in body. Punica granatum Linnaeus (Lythraceae), pomegranate, is a fruit with antidiabetic potential. Oleanolic acid (OA), ursolic acid (UA), and gallic acid (GA) are the major bioactive components of pomegranate. Co-administration of these compounds with other drugs could result in altered drug pharmacokinetics, possibly due to competing for transporter proteins.
  
  
  OBJECTIVE
  We investigated the interactions of these three compounds with the essential hepatic and renal SLC transporters.
  
  
  METHODS
  Uptake of radiolabeled transporter model substrates was assessed in HEK293 cells over-expressing SLC transporters including the organic anion transporters (OATs), organic anion transporting polypeptides (OATPs) and organic cation transporters (OCTs), in the presence or absence of 10.0 µM UA, OA, or GA. Their IC50 values on specific SLC transporters were also evaluated using varying concentrations of the particular compound (ranging from 0.10 nM to 80.0 µM).
  
  
  RESULTS
  Our results demonstrated UA could significantly inhibit OAT3 and OATP2B1 uptake (IC50: 18.9 ± 8.20 µM and 11.0 ± 5.00 µM, respectively) and GA has a pronounced inhibitory effect on OATP1B3 uptake (IC50: 1.60 ± 0.60 μM).
  
  
  CONCLUSIONS
  Our study reports the interactions of OA, UA, and GA with the essential SLC transporters. This information may contribute to elucidating the drug-drug/herb interactions involved with these three compounds and form the basis of therapeutic optimization when drugs are co-administered.
authors.affiliation: Faculty of Pharmacy, University of Sydney , NSW , Australia .
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.forename: Florence Shin Gee
authors.initials: FS
authors.lastname: Cheung
authors.forename: Ting
authors.initials: T
authors.lastname: Chan
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
authors.forename: Fanfan
authors.initials: F
authors.lastname: Zhou
mesh_terms: D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D057809:HEK293 Cells; D041743:Herb-Drug Interactions; D006801:Humans; D020128:Inhibitory Concentration 50; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D029561:Lythraceae / Q000737:chemistry*; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors; D014315:Triterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D005707:Gallic Acid; D009828:Oleanolic Acid; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: Drug–drug/herb interaction; gallic acid; oleanolic acid; ursolic acid