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

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...

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Autores principales: Yan, Jingjing, He, Xin, Feng, Shan, Zhai, Yiran, Ma, Yetao, Liang, Sheng, Jin, Chunhuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150957/
https://www.ncbi.nlm.nih.gov/pubmed/25134417
http://dx.doi.org/10.1186/1472-6882-14-306
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author Yan, Jingjing
He, Xin
Feng, Shan
Zhai, Yiran
Ma, Yetao
Liang, Sheng
Jin, Chunhuan
author_facet Yan, Jingjing
He, Xin
Feng, Shan
Zhai, Yiran
Ma, Yetao
Liang, Sheng
Jin, Chunhuan
author_sort Yan, Jingjing
collection PubMed
description 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.
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spelling pubmed-41509572014-09-03 Up-regulation on cytochromes P450 in rat mediated by total alkaloid extract from Corydalis yanhusuo Yan, Jingjing He, Xin Feng, Shan Zhai, Yiran Ma, Yetao Liang, Sheng Jin, Chunhuan BMC Complement Altern Med Research Article 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. BioMed Central 2014-08-18 /pmc/articles/PMC4150957/ /pubmed/25134417 http://dx.doi.org/10.1186/1472-6882-14-306 Text en © 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.
spellingShingle Research Article
Yan, Jingjing
He, Xin
Feng, Shan
Zhai, Yiran
Ma, Yetao
Liang, Sheng
Jin, Chunhuan
Up-regulation on cytochromes P450 in rat mediated by total alkaloid extract from Corydalis yanhusuo
title Up-regulation on cytochromes P450 in rat mediated by total alkaloid extract from Corydalis yanhusuo
title_full Up-regulation on cytochromes P450 in rat mediated by total alkaloid extract from Corydalis yanhusuo
title_fullStr Up-regulation on cytochromes P450 in rat mediated by total alkaloid extract from Corydalis yanhusuo
title_full_unstemmed Up-regulation on cytochromes P450 in rat mediated by total alkaloid extract from Corydalis yanhusuo
title_short Up-regulation on cytochromes P450 in rat mediated by total alkaloid extract from Corydalis yanhusuo
title_sort up-regulation on cytochromes p450 in rat mediated by total alkaloid extract from corydalis yanhusuo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150957/
https://www.ncbi.nlm.nih.gov/pubmed/25134417
http://dx.doi.org/10.1186/1472-6882-14-306
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