期刊
JOURNAL OF ETHNOPHARMACOLOGY
卷 146, 期 3, 页码 734-743出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2013.01.028
关键词
Schisandra chinensis; Vinegar-processed; CYP450; Pharmacokinetic; Cocktail; mRNA; Real-time RT-PCR
资金
- Major Program of State Commission of Science Technology of China [2009ZX09308-004]
- Educational Commission of Jiangsu Province of China [09KJA360001]
- Key Laboratory of Acupuncture of Jiangsu Province of China [KJA200906]
- Technology Project of Nanjing University of Chinese Medicine of China [10XJC06]
- Preponderant discipline of Jiangsu province [2011ZYX2-003]
Ethnopharmacological relevance: Schisandra chinensis (SC) is a well-known traditional Chinese herbal medicine that has been used in clinical practices for thousands of years. However, the differences between the effects of unprocessed and vinegar-processed Schisandra chinensis (VSC) on cytochrome P450 (CYP450) activities are poorly understood. Aim of the study: To evaluate the differences between processed and unprocessed SC on the metabolism of CYP1A2, CYP2E1 and CYP3A4 substrates in rats using a cocktail method based on a developed and validated HPLC method. We also investigate the influence of processing on the levels of CYP mRNA. Materials and methods: Three probe substrates (theophylline, dapsone and chlorzoxazone) were delivered simultaneously into rats treated with single or multiple doses of processed or unprocessed SC extract. The plasma concentrations of the three probes were profiled by HPLC, and their corresponding pharmacokinetic parameters were calculated. Real-time RT-PCR was performed to determine the effects of processed and unprocessed SC on the mRNA expression of CYP1A2, CYP2E1 and CYP3A4 in the liver. Results: Treatment with single or multiple doses of either extract of SC induced CYP3A4 enzyme activity and inhibited CYP1A2 enzyme activity in rats. Furthermore, the inhibitory effect of SC was more potent after vinegar processing than without vinegar processing. CYP2E1 enzyme activity was induced after treatment with a single dose but was inhibited after multiple doses. The mRNA expression results were in accordance with the pharmacokinetic results. Conclusions: These results provide useful scientific data for the safe clinical application of either extract of SC in combination with other drugs, which should lack the side effects induced by other herb-drug interactions. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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