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Metabolism and permeability of curcumin in cultured C aco‐2 cells
Author(s) -
Dempe Julia S.,
Scheerle Romy K.,
Pfeiffer Erika,
Metzler Manfred
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200113
Subject(s) - curcumin , bioavailability , chemistry , in vivo , metabolite , caco 2 , metabolism , glucuronide , in vitro , glucuronidation , conjugate , biochemistry , glucuronic acid , pharmacology , gastrointestinal tract , microsome , biology , mathematical analysis , mathematics , polysaccharide , microbiology and biotechnology
Scope Curcumin ( CUR ) and its major metabolite hexahydro‐ CUR were studied in C aco‐2 cells and in the C aco‐2 M illicell® system in vitro to simulate their in vivo intestinal metabolism and absorption in humans. Methods and results Analysis of the incubation medium and cell lysate showed that C aco‐2 cells reduce CUR to hexahydro‐ CUR and octahydro‐ CUR , and conjugate CUR and its reductive metabolites with glucuronic acid and sulfate. Using the C aco‐2 M illicell® 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 ( P app 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. Conclusion 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.