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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zhou, Hui Shi, Rong Ma, Bingliang Ma, Yueming Wang, Changhong Wu, Dazheng Wang, Xinhong Cheng, Nengneng |
| Description | Country affiliation: China Author Affiliation: Zhou H ( Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, China.) |
| Abstract | 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 to determine 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 inhibited significantly by furafylline and predominantly catalysed by recombinant CYP1A2, whereas glucuronidation was inhibited by silibinin, quercetin, as well as 1-naphthol and catalysed by recombinant UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9 and UGT1A10. These results showed that jatrorrhizine is metabolized by human CYP1A2 and multiple UGT1A isoforms. |
| File Format | HTM / HTML |
| ISSN | 01422782 |
| Issue Number | 3 |
| Volume Number | 34 |
| e-ISSN | 1099081X |
| Journal | Biopharmaceutics & Drug Disposition |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2013-04-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Pharmacology Berberine Analogs & Derivatives Cytochrome P-450 Cyp1a2 Metabolism Glucuronosyltransferase Microsomes, Liver Cytochrome P-450 Cyp1a2 Inhibitors Enzyme Inhibitors Pharmacology Gastrointestinal Agents Glucuronides Antagonists & Inhibitors Humans Protein Isoforms Recombinant Proteins Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmacology (medical) Pharmaceutical Science |
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