Effects of Baoyuan decoction, a traditional Chinese medicine formula, on the activities and mRNA expression of seven CYP isozymes in rats

Baoyuan decoction (BYD), a traditional Chinese medicine (TCM) formula, is composed of four herbs and widely used with western drugs to treat coronary heart disease, aplastic anemia and chronic renal failure in clinic. However, no study of the effect of BYD on the cytochrome P450 (CYP) activities has...

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Bibliographic Details
Published in:Journal of ethnopharmacology 2018-10, Vol.225, p.327-335
Main Authors: Lu, Ying-Yuan, Du, Zhi-Yong, Li, Yan, Wang, Jin-Long, Zhao, Ming-Bo, Jiang, Yong, Guo, Xiao-Yu, Tu, Peng-Fei
Format: Article
Language:English
Subjects:
Animals
Baoyuan decoction (BYD)
Cocktail probe drugs
Cytochrome P-450 Enzyme Inducers - pharmacokinetics
Cytochrome P-450 Enzyme Inducers - pharmacology
Cytochrome P-450 Enzyme Inhibitors - pharmacokinetics
Cytochrome P-450 Enzyme Inhibitors - pharmacology
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
Cytochrome P450 (CYP)
Drugs, Chinese Herbal - chemistry
Drugs, Chinese Herbal - pharmacology
Enzyme Induction - drug effects
Herb-drug interaction (HDI)
Isoenzymes - genetics
Isoenzymes - metabolism
Male
Medicine, Chinese Traditional
mRNA
Rats, Sprague-Dawley
RNA, Messenger - metabolism
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Summary:Baoyuan decoction (BYD), a traditional Chinese medicine (TCM) formula, is composed of four herbs and widely used with western drugs to treat coronary heart disease, aplastic anemia and chronic renal failure in clinic. However, no study of the effect of BYD on the cytochrome P450 (CYP) activities has been reported. The purpose of the present study was to evaluate the potential influences of BYD on the activities of seven CYP isozymes (CYP1A2, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4) in rats. A sensitive and selective UPLC-MS/MS method for simultaneous determination of seven probe drugs and internal standard (IS) in rat plasma was developed and validated. The influence of BYD on the activities of CYP isozymes and mRNA expression levels were carried out by comparing plasma pharmacokinetics and real-time reverse transcription-polymerase chain reaction (RT-PCR) of probe drugs between control and BYD treatment groups respectively. The calibration curve were linear, with correlation coefficient (r) > 0.99 for seven probe drugs. The intra and inter-assay accuracy and precision of the method were within ± 14.9% and the recoveries ranged from 83.2% to 106.1%. Compared with control group, BYD at low (1.46 g/kg) and high (7.30 g/kg) dosages could significantly increase Cmax and AUC0-t of chlorzoxazone and testosterone, while decrease AUC0-t of phenacetin at high dosage and increase AUC0-t of tolbutamide and metoprolol. Additionally, BYD had increased AUC0-t of bupropion at low dosage and decreased it at high dosage. The mRNA expression results were in accordance with those of pharmacokinetic. BYD exhibited inhibitory effects on CYP2C9, CYP2E1, and CYP3A4. Moreover, BYD had induction effects on CYP1A2, and CYP2D6 activities. However, no significant change in CYP2C19 activity was observed. It would be useful for the safe and effective usage of BYD in clinic. [Display omitted]
ISSN:0378-8741
1872-7573
DOI:10.1016/j.jep.2018.07.023