<Emphasis Type="Italic">In Vitro</Emphasis> metabolism of Jaceosidin and characterization of cytochrome P450 and UDP-glucuronosyltransferase enzymes in human liver microsomes |
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Authors: | Won Young Song Hye Young Ji Nam-In Baek Tae-Sook Jeong Hye Suk Lee |
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Institution: | (1) Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb, P.O. Box 5400, Mail Stop 17-12, Princeton, New Jersey 08543-5400, USA;(2) Department of Metabolism and Pharmacokinetics, AstraZeneca, Waltham, Massachusett 02451, USA |
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Abstract: | Jaceosidin is an active component in Artemisia species as well as Eupatorium species and it exhibits antiallergic, anticancer, antioxidant, anti-inflammatory, and antimutagenic activities. Jaceosidin
was metabolized to jaceosidin glucuronide, 6-O-desmethyljaceosidin, hydroxyjaceosidin, 6-O-desmethyljaceosidin glucuronide, and hydroxyjaceosidin glucuronide in human liver microsomes. This study characterized the
human liver cytochrome P450 (CYP) and UDPglucuronosyltransferase (UGT) enzymes responsible for the metabolism of jaceosidin.
CYP1A2 was identified as the major enzyme responsible for the formation of 6-O-desmethyljaceosidin and hydroxyjaceosidin from jaceosidin on the basis of a combination of correlation analysis and experiments
including immuno-inhibition, chemical inhibition in human liver microsomes, and metabolism by human cDNA-expressed CYP enzymes.
Jaceosidin glucuronidation was catalyzed by UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9, and UGT1A10. These results suggest that
the pharmacokinetics of jaceosidin may be dramatically affected by polymorphic CYP1A2, UGT1A1, and UGT1A7 responsible for
the metabolism of jaceosidin or by the coadministration of relevant CYP1A2 or UGT inhibitors or inducers. |
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