Biliary excretion of curcumin is mediated by multidrug resistance-associated protein 2

Biol Pharm Bull. 2012;35(5):777-80. doi: 10.1248/bpb.35.777.

Abstract

Curcumin has a wide spectrum of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer properties. Recently, its potential as effective chemoprevention against cholangiocarcinoma, a highly malignant tumor of the bile duct with limited therapeutic options, was reported. The purpose of the present study was to investigate the contribution of multidrug resistance-associated protein 2 (Mrp2) to the biliary excretion of curcumin using Sprague-Dawley rats (SDR) and Eisai hyperbilirubinemic rats (EHBR). After intravenous administration of curcumin with a loading dose of 4.5 mg/kg, followed by a constant infusion of 18 mg/kg/h to the SDR and EHBR, the pharmacokinetic parameters of curcumin were estimated. In EHBR, the total area under the bile concentration-time curve from 0 to 80 min following curcumin administration was dramatically decreased (0.094%) compared to that in SDR. In addition, the plasma-to-bile and liver-to-bile clearances were both significantly decreased compared to SDR. These results provide the first evidence that Mrp2 mediates the biliary excretion of curcumin and thus may be a major factor in the control of exposure of curcumin to the bile duct. This study may be helpful to the potential use of curcumin as a treatment for bile duct cancer, and to understanding the genetic polymorphism of Mrp2 for clinical trials of curcumin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile / metabolism*
  • Bile Duct Neoplasms* / drug therapy
  • Bile Duct Neoplasms* / metabolism
  • Bile Ducts, Intrahepatic
  • Biliary Tract / metabolism*
  • Cholangiocarcinoma* / drug therapy
  • Cholangiocarcinoma* / metabolism
  • Curcuma / chemistry
  • Curcumin / administration & dosage
  • Curcumin / pharmacokinetics*
  • Curcumin / therapeutic use
  • Hyperbilirubinemia / metabolism
  • Liver / metabolism
  • Male
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Phytotherapy
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacokinetics*
  • Plant Extracts / therapeutic use
  • Plasma / metabolism
  • Polymorphism, Genetic
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Multidrug Resistance-Associated Proteins
  • Plant Extracts
  • multidrug resistance-associated protein 2
  • Curcumin