Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 51, Issue 8, Pages 932-938Publisher
WILEY
DOI: 10.1002/mnfr.200600283
Keywords
curcumin; glucuronidation; microsomes; UGTs
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Glucuronidation is an important pathway in the metabolism of curcumin, but the isoforms of uridine5'-diphosphoglucuronosyltransferase (UGT) involved are not known. Here, we report on the glucuronidation of the three natural curcurninoids and their major phase I metabolites with microsomes from human liver and intestine as well as with human recombinant UGTs. Microsornes from human liver generated predominantly the phenolic and small amounts of the alcoholic glucuronide of each curcuminoid, whereas intestinal microsornes formed only the phenolic conjugates but with higher activities. The phenolic glucuronidation of the curcurninoids was predominantly catalyzed by hepatic UGT1A1 and intestinal UGT1A8 and 1A10, whereas UGTIA9, 2B7, and 1A8 exhibited high activities for hexahydro-curcuminoids. UGTIA9 was able to form the alcoholic glucuronide of each curcuminoid in addition to the phenolic conjugate. These data suggest that the gastrointestinal tract contributes substantially to the glucuronidation of curcurninoids in humans, which may have important implications for their pharmacokinetic fate in vivo.
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