In vitro metabolism of 4, 5-dimethoxycanthin-6-one by human liver microsomes and its inhibition on human CYP1A2
| Autor: | Xiaolei Miao, Junjun Wang, Jiaojiao You, Yong Chen |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Cytochrome P-450 CYP1A2 Inhibitors
Metabolite In Vitro Techniques Pharmacology 030226 pharmacology & pharmacy 01 natural sciences General Biochemistry Genetics and Molecular Biology Inhibitory Concentration 50 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cytochrome P-450 Enzyme System Cytochrome P-450 CYP1A2 medicine Humans General Pharmacology Toxicology and Pharmaceutics chemistry.chemical_classification biology CYP3A4 Plant Extracts CYP1A2 Cytochrome P450 General Medicine Metabolism 0104 chemical sciences 010404 medicinal & biomolecular chemistry Enzyme Biochemistry chemistry Phenacetin Picrasma Microsomes Liver biology.protein Microsome Carbolines medicine.drug |
| Zdroj: | Life Sciences. 190:46-51 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2017.09.031 |
| Popis: | Aims P. quassioides is a traditional Chinese medicine used for the treatment of gastroenteritis, snakebite, infection and hypertension in China. 4, 5-dimethoxycanthin-6-one is one of the main active canthinone alkaloid isolated from P. quassioides . The aim of this work was to identify the cytochrome P (CYP) 450 enzymes responsible for the metabolism of 4, 5-dimethoxycanthin-6-one (DCO) and to evaluate the inhibitory effect of DCO on CYP activity in human liver microsomes (HLM) in vitro . Materials and methods the CYP isoforms responsible for DCO metabolism and the inhibitory effects of DCO on CYP activity was studied in HLM. Key findings The in vitro metabolic enzyme of DCO was CYP3A4 (mediated the formation of metabolites M1-M5), CYP2C9 (mediated the formation of metabolites M1-M3, M6 and M8) and CYP2D6 (mediated the formation of metabolite M3) in HLM. Furthermore, the present work found that DCO uncompetitively inhibited CYP1A2-mediated phenacetin O-deethylation with an IC 50 value of 1.7 μM and a Ki value of 2.6 μM. Significance The results suggested that the metabolic interaction should be existed when the substrate drugs of CYP1A2 were co-administered with DCO or traditional Chinese medicine containing it, such as the extract of P. quassioides and Kumu injection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect