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| Evaluation of the effect of psoralen on human cytochrome P450 subunit activities by Cocktail invitro probe method |
| Hits 1625 Download times 1133 Received:September 05, 2018 |
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| DOI
10.11656/j.issn.1673-9043.2018.06.13 |
| Key Words
cocktail;psoralen;CYP450;probe drugs |
| Author Name | Affiliation | E-mail | | ZHANG Wenjie | Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China | | | LI Mengrong | Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China | | | HAN Lifeng | Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China | | | HAO Jia | Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China | | | LIU Erwei | Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China | liuwei628@hotmail.com |
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| Abstract
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| [Objective] By using "Cocktail" probe method in vitro to determinate the effect of psoralen, which is the effective components of fructus psoraleae, on the activities of human liver microsomal enzymes subtype. It would provide strong evidence for the clinical safety of combination psoralen with other medicine.[Methods] Establish a method for simultaneous determination of seven types of the metabolites of probe drugs by liquid chromatography-mass spectrometry (LC-MS/MS). Throughing the effects of psoralen on CYP450 enzyme isoforms by cocktail probe experiments in vitro to investigate the effect of psoralen on metabolism of human liver.[Results] The established LC-MS/MS method was precise and credible; it was complied with the requirements for the determination of biological samples, and could be used for the quantitative analysis of the metabolites of CYP450 probe in human liver microsomes. Compared with the blank group, the transformation rate of the psoralen group on each CYP450 substrate decreased. The conversion rate of coumarin decreased most significantly and the inhibition rate was 95.84%. However, the decreasion of taxol was not obvious, and the inhibition rate was only 10.39%. The inhibition rate of psoralen on the other substrate was between 82%~91%.[Conclusion] Psoralen had inhibitory effects on subtypes of human liver microsomal CYP1A2, 2A6, 2C8, 2C9, 2D6, 2E1 and 3A4, the influence on CYP2A6, and the inhibition rate of 1A2 and 2D6 were much significantly. These results showed that psoralen had different effects on different subtypes of human liver microsomal enzymes, which indicated us to pay attention to the safety of drug combination when long-term administration of psoralen. |
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