Up-regulation on cytochromes P450 in rat mediated by total alkaloid extract from Corydalis yanhusuo

BMC Complementary and Alternative Medicine

Research Article

Sheng Liang¹  Jingjing Yan¹  Yiran Zhai¹  Chunhuan Jin¹  Shan Feng¹  Yetao Ma¹  Xin He² 

[1] School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, 300193, Tianjin, Nankai District, China;School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, 300193, Tianjin, Nankai District, China;Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, 300193, Tianjin, Nankai District, China;

关键词: Total alkaloid extract;    Cytochromes P450;    Histopathology;    Enzyme activity;    mRNA level;    Herb (drug)-drug interaction;   

DOI  :  10.1186/1472-6882-14-306

 received in 2014-03-03, accepted in 2014-08-05,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundYanhusuo (Corydalis yanhusuo W.T. Wang; YHS), is a well-known traditional Chinese herbal medicine, has been used in China for treating pain including chest pain, epigastric pain, and dysmenorrhea. Its alkaloid ingredients including tetrahydropalmatine are reported to inhibit cytochromes P450 (CYPs) activity in vitro. The present study is aimed to assess the potential of total alkaloid extract (TAE) from YHS to effect the activity and mRNA levels of five cytochromes P450 (CYPs) in rat.MethodsRats were administered TAE from YHS (0, 6, 30, and 150 mg/kg, daily) for 14 days, alanine aminotransferase (ALT) levels in serum were assayed, and hematoxylin and eosin-stained sections of the liver were prepared for light microscopy. The effects of TAE on five CYPs activity and mRNA levels were quantitated by cocktail probe drugs using a rapid chromatography/tandem mass spectrometry (LC-MS/MS) method and reverse transcription-polymerase chain reaction (RT-PCR), respectively.ResultsIn general, serum ALT levels showed no significant changes, and the histopathology appeared largely normal compared with that in the control rats. At 30 and 150 mg/kg TAE dosages, an increase in liver CYP2E1 and CYP3A1 enzyme activity were observed. Moreover, the mRNA levels of CYP2E1 and CYP3A1 in the rat liver, lung, and intestine were significantly up-regulated with TAE from 6 and 30 mg/kg, respectively. Furthermore, treatment with TAE (150 mg/kg) enhanced the activities and the mRNA levels of CYP1A2 and CYP2C11 in rats. However, the activity or mRNA level of CYP2D1 remained unchanged.ConclusionsThese results suggest that TAE-induced CYPs activity in the rat liver results from the elevated mRNA levels of CYPs. Co-administration of prescriptions containing YHS should consider a potential herb (drug)–drug interaction mediated by the induction of CYP2E1 and CYP3A1 enzymes.

【 授权许可】

Unknown   
© Yan et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.