Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 57, Issue 9, Pages 1543-1549Publisher
WILEY-BLACKWELL
DOI: 10.1002/mnfr.201200113
Keywords
Caco-2 cells; Curcumin; Hexahydrocurcumin; Metabolism; Permeability
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Scope Curcumin(CUR) and its major metabolite hexahydro-CUR were studied in Caco-2 cells and in the Caco-2 Millicell (R) system in vitro to simulate their in vivo intestinal metabolism and absorption in humans. Methods and resultsAnalysis 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 (R) 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. ConclusionThe 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.
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