Document Detail

CYP450 1A2 and multiple UGT1A isoforms are responsible for jatrorrhizine metabolism in human liver microsomes.
MedLine Citation:
PMID:  23299247     Owner:  NLM     Status:  Publisher    
Jatrorrhizine, one of the protoberberine alkaloids derived from the plant Coptis chinensis, is expected to be developed as a new gastric prokinetic drug, but its metabolic characteristics in humans remain unknown. This study characterized the phase I and phase II metabolites, metabolic kinetics, and cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes responsible for the metabolism of jatrorrhizine in human liver microsomes (HLMs). Chemical inhibition in HLMs and metabolism by recombinant human CYP or UGT enzymes were employed for determining the key metabolic enzyme subtypes. In HLMs, demethyleneberberine (demethylated product) and jatrorrhizine glucuronide were identified as the phase I and phase II metabolites, respectively. The enzyme kinetics for both demethylation and glucuronidation were fitted to the Michaelis-Menten equation. Demethylation was significantly inhibited by furafylline and predominantly catalyzed by recombinant CYP1A2, whereas glucuronidation was inhibited by silibinin, quercetin, as well as 1-naphthol and catalyzed by recombinant UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9, and UGT1A10. These results showed that jatrorrhizine is metabolized by human CYP1A2 and multiple UGT1A isoforms. Copyright © 2013 John Wiley & Sons, Ltd.
Hui Zhou; Rong Shi; Bingliang Ma; Yueming Ma; Changhong Wang; Dazheng Wu; Xinhong Wang; Nengneng Cheng
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-9
Journal Detail:
Title:  Biopharmaceutics & drug disposition     Volume:  -     ISSN:  1099-081X     ISO Abbreviation:  Biopharm Drug Dispos     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7911226     Medline TA:  Biopharm Drug Dispos     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 John Wiley & Sons, Ltd.
Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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