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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Li, Xin Wang, Kai Wei, Wei Liu, Yong-yu Gong, Lu |
| Description | Country affiliation: China Author Affiliation: Li X ( Tianjin Medical University General Hospital, Department of Infectious Diseases and Immunology, Tianjin, 300052, China.) |
| Abstract | Brucine, one of the main active ingredients in semen Strychni, has been included in many oral prescriptions of traditional Chinese medicine. In this study, we investigated the in vitro metabolism of brucine by human liver microsomes (HLMs) and the metabolic interactions of brucine with the substrates of cytochrome P450 (CYP450). Brucine was incubated with HLMs or CYP3A4 and then analysed by Liquid chromatography/mass spectrometry. The Km and Vmax values for HLMs were 30.53±3.14µM and 0.08±0.0029nmol/mg protein/min, respectively, while the corresponding values for CYP3A4 were 20.12±3.05µM and 6.40±0.21nmol/nmol P450/min. CYP3A4 may be the major enzyme responsible for brucine metabolism in HLMs, other human isoforms of CYP showed minimal or no effect on brucine metabolism. The inhibitory action of brucine was observed in CYP3A4 for the 1'-hydroxylation of midazolam, with inhibitory concentration 50 (IC50) of 8.4-fold higher than specific inhibitors in HLMs. Furthermore, brucine significantly inhibited the CYP3A4-catalyzed midazolam 1'-hydroxylation (Ki=2.14µM) at a concentration lower than 10µM, but no obvious inhibitory effects were observed on other CYP substrates (IC50>50µM). These results suggest that brucine has the potential to interact with a wide range of xenobiotics and endogenous chemicals especially CYP3A4 substrates. |
| File Format | HTM / HTML |
| ISSN | 00092797 |
| Issue Number | 3 |
| Volume Number | 204 |
| e-ISSN | 18727786 |
| Journal | Chemico-Biological Interactions |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2013-08-25 |
| Publisher Place | Ireland |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Biochemistry Discipline Pharmacology Cytochrome P-450 Cyp3a Metabolism Drugs, Chinese Herbal Microsomes, Liver Strychnine Analogs & Derivatives Biological Assay Cells, Cultured Chemistry Enzyme Activation Drug Effects Enzyme Inhibitors Pharmacokinetics Humans Hydroxylation Inhibitory Concentration 50 Kinetics Midazolam Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Toxicology |
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