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Protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice
BACKGROUND: Dehydroandrographolide (DA) is the main contributor to the therapeutic properties of the medicinal plant Andrographis paniculata (AP). However, it is unknown whether DA has a hepatoprotective effect on obstructive cholestasis in mice and humans. METHODS: We administered DA to mice for 5...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675681/ https://www.ncbi.nlm.nih.gov/pubmed/29152129 http://dx.doi.org/10.18632/oncotarget.21233 |
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author | Weng, Zhiyong Liu, Xuefeng Hu, Jiehua Mu, Jingzhou Xie, Jing Yao, Chenjuan Li, Lihua |
author_facet | Weng, Zhiyong Liu, Xuefeng Hu, Jiehua Mu, Jingzhou Xie, Jing Yao, Chenjuan Li, Lihua |
author_sort | Weng, Zhiyong |
collection | PubMed |
description | BACKGROUND: Dehydroandrographolide (DA) is the main contributor to the therapeutic properties of the medicinal plant Andrographis paniculata (AP). However, it is unknown whether DA has a hepatoprotective effect on obstructive cholestasis in mice and humans. METHODS: We administered DA to mice for 5 days prior to bile duct ligation (BDL) and for the 7 days. Liver function markers, liver histology and necrosis, compensatory responses of hepatocytes, liver fibrosis and the expression of hepatic fibrogenesis markers were evaluated in BDL mice and/or human LX-2 cells. RESULTS: Mice treated with DA demonstrated lower levels of serum alanine transarninase (ALT), milder liver damage, liver necrosis and fibrosis formation than in vehicle control with carboxymethylcellulose (CMC) mice after BDL. DA treatment also enhanced the Mrp3 expression of hepatocytes but not Mrp4 following BDL. Further, DA treatment in BDL mice significantly reduced liver mRNA and/or protein expression of Tgf-β, Col1a1, α-Sma and Mmp2. This result was also supported by hydroxyproline analysis. The molecular mechanisms of DA treatment were also assessed in human hepatic stellate cell line (LX-2 cell). DA treatment significantly inhibited Tgf-β-induced Col1a1, Mmp2 and α-Sma expression in human LX-2 cells. These data suggested that DA treatment reduced liver damage through development of a hepatic adaptive response and inhibition of the activation of HSCs, which led to a reduction in liver fibrosis formation in BDL mice. CONCLUSIONS: DA treatment protected against liver damage and fibrosis following BDL and might be an effective therapy for extrahepatic cholestasis due to bile duct obstruction. |
format | Online Article Text |
id | pubmed-5675681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56756812017-11-18 Protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice Weng, Zhiyong Liu, Xuefeng Hu, Jiehua Mu, Jingzhou Xie, Jing Yao, Chenjuan Li, Lihua Oncotarget Research Paper BACKGROUND: Dehydroandrographolide (DA) is the main contributor to the therapeutic properties of the medicinal plant Andrographis paniculata (AP). However, it is unknown whether DA has a hepatoprotective effect on obstructive cholestasis in mice and humans. METHODS: We administered DA to mice for 5 days prior to bile duct ligation (BDL) and for the 7 days. Liver function markers, liver histology and necrosis, compensatory responses of hepatocytes, liver fibrosis and the expression of hepatic fibrogenesis markers were evaluated in BDL mice and/or human LX-2 cells. RESULTS: Mice treated with DA demonstrated lower levels of serum alanine transarninase (ALT), milder liver damage, liver necrosis and fibrosis formation than in vehicle control with carboxymethylcellulose (CMC) mice after BDL. DA treatment also enhanced the Mrp3 expression of hepatocytes but not Mrp4 following BDL. Further, DA treatment in BDL mice significantly reduced liver mRNA and/or protein expression of Tgf-β, Col1a1, α-Sma and Mmp2. This result was also supported by hydroxyproline analysis. The molecular mechanisms of DA treatment were also assessed in human hepatic stellate cell line (LX-2 cell). DA treatment significantly inhibited Tgf-β-induced Col1a1, Mmp2 and α-Sma expression in human LX-2 cells. These data suggested that DA treatment reduced liver damage through development of a hepatic adaptive response and inhibition of the activation of HSCs, which led to a reduction in liver fibrosis formation in BDL mice. CONCLUSIONS: DA treatment protected against liver damage and fibrosis following BDL and might be an effective therapy for extrahepatic cholestasis due to bile duct obstruction. Impact Journals LLC 2017-09-23 /pmc/articles/PMC5675681/ /pubmed/29152129 http://dx.doi.org/10.18632/oncotarget.21233 Text en Copyright: © 2017 Weng et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Weng, Zhiyong Liu, Xuefeng Hu, Jiehua Mu, Jingzhou Xie, Jing Yao, Chenjuan Li, Lihua Protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice |
title | Protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice |
title_full | Protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice |
title_fullStr | Protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice |
title_full_unstemmed | Protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice |
title_short | Protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice |
title_sort | protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675681/ https://www.ncbi.nlm.nih.gov/pubmed/29152129 http://dx.doi.org/10.18632/oncotarget.21233 |
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