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Open Access Research article

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

Jingjing Yan1, Xin He12*, Shan Feng1, Yiran Zhai1, Yetao Ma1, Sheng Liang1 and Chunhuan Jin1

Author Affiliations

1 School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Tianjin 300193, Nankai District, China

2 Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, Tianjin 300193, Nankai District, China

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BMC Complementary and Alternative Medicine 2014, 14:306  doi:10.1186/1472-6882-14-306

Published: 18 August 2014

Abstract

Background

Yanhusuo (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.

Methods

Rats 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.

Results

In 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.

Conclusions

These 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.

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