title: Metabolism and permeability of curcumin in cultured Caco-2 cells.
abstract: METHODS
  Curcumin (CUR) and its major metabolite hexahydro-CUR were studied in Caco-2 cells and in the Caco-2 Millicell® system in vitro to simulate their in vivo intestinal metabolism and absorption in humans.
  
  
  RESULTS
  Analysis of the incubation medium and cell lysate showed that Caco-2 cells reduce CUR to hexahydro-CUR and octahydro-CUR, and conjugate CUR and its reductive metabolites with glucuronic acid and sulfate. Using the Caco-2 Millicell® system, an efficient transfer of the conjugates into the basolateral, but not the apical, compartment was observed after apical administration. Likewise, hexahydro-CUR was reduced to octahydro-CUR, and glucuronide and sulfate conjugates almost exclusively permeated to the basolateral side. The apparent permeability coefficients (Papp values) of CUR, hexahydro-CUR and their metabolites were determined and found to be extremely low for unchanged CUR, but somewhat higher for hexahydro-CUR and the conjugated metabolites.
  
  
  CONCLUSIONS
  The results of this study clearly show that the systemic bioavailability of CUR from the intestine after oral intake must be expected to be virtually zero. Reductive and conjugated metabolites, formed from CUR in the intestine, exhibit moderate absorption. Thus, any biological effects elicited by CUR in tissues other than the gastrointestinal tract are likely due to CUR metabolites.
authors.affiliation: Institute of Applied Biosciences, Chair of Food Chemistry, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
authors.forename: Julia S
authors.initials: JS
authors.lastname: Dempe
authors.forename: Romy K
authors.initials: RK
authors.lastname: Scheerle
authors.forename: Erika
authors.initials: E
authors.lastname: Pfeiffer
authors.forename: Manfred
authors.initials: M
authors.lastname: Metzler
mesh_terms: D000042:Absorption; D001682:Biological Availability; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000493:pharmacokinetics*; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology* / Q000187:drug effects
chemical_list: D003474:Curcumin