Cargando…

Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress/GSK-3-mediated mitochondrial pathway

Herbal medicine as an alternative approach in the treatment of disease has drawn growing attention. Identification of the active ingredient is needed for effective utilization of the herbal medicine. Licorice is a popular herbal plant that is widely used to treat various diseases including liver dis...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Enxiang, Yin, Shutao, Song, Xinhua, Fan, Lihong, Hu, Hongbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5128870/
https://www.ncbi.nlm.nih.gov/pubmed/27901086
http://dx.doi.org/10.1038/srep38138
_version_ 1782470492177825792
author Zhang, Enxiang
Yin, Shutao
Song, Xinhua
Fan, Lihong
Hu, Hongbo
author_facet Zhang, Enxiang
Yin, Shutao
Song, Xinhua
Fan, Lihong
Hu, Hongbo
author_sort Zhang, Enxiang
collection PubMed
description Herbal medicine as an alternative approach in the treatment of disease has drawn growing attention. Identification of the active ingredient is needed for effective utilization of the herbal medicine. Licorice is a popular herbal plant that is widely used to treat various diseases including liver diseases. Glycycoumarin (GCM) is a representative of courmarin compounds isolated from licorice. In the present study, the protective effect of GCM on hepatocyte lipoapoptosis has been evaluated using both cell culture model of palmitate-induced lipoapoptosis and animal model of non-alcoholic steatohepatitis (NASH). The results demonstrated for the first time that GCM was highly effective in suppressing hepatocyte lipoapoptosis in both in vitro and in vivo. Mechanistically, GCM was able to re-activate the impaired autophagy by lipid metabolic disorders. In line with the activation of autophagy, ER stress-mediated JNK and mitochondrial apoptotic pathway activation was inhibited by GCM both in vitro and in vivo. In addition, inactivation of GSK-3 might also contribute to the protective effect of GCM on hepatocyte lipoapoptosis. Our findings supported GCM as a novel active component of licorice against non-alcoholic fatty liver disease (NAFLD).
format Online
Article
Text
id pubmed-5128870
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-51288702016-12-15 Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress/GSK-3-mediated mitochondrial pathway Zhang, Enxiang Yin, Shutao Song, Xinhua Fan, Lihong Hu, Hongbo Sci Rep Article Herbal medicine as an alternative approach in the treatment of disease has drawn growing attention. Identification of the active ingredient is needed for effective utilization of the herbal medicine. Licorice is a popular herbal plant that is widely used to treat various diseases including liver diseases. Glycycoumarin (GCM) is a representative of courmarin compounds isolated from licorice. In the present study, the protective effect of GCM on hepatocyte lipoapoptosis has been evaluated using both cell culture model of palmitate-induced lipoapoptosis and animal model of non-alcoholic steatohepatitis (NASH). The results demonstrated for the first time that GCM was highly effective in suppressing hepatocyte lipoapoptosis in both in vitro and in vivo. Mechanistically, GCM was able to re-activate the impaired autophagy by lipid metabolic disorders. In line with the activation of autophagy, ER stress-mediated JNK and mitochondrial apoptotic pathway activation was inhibited by GCM both in vitro and in vivo. In addition, inactivation of GSK-3 might also contribute to the protective effect of GCM on hepatocyte lipoapoptosis. Our findings supported GCM as a novel active component of licorice against non-alcoholic fatty liver disease (NAFLD). Nature Publishing Group 2016-11-30 /pmc/articles/PMC5128870/ /pubmed/27901086 http://dx.doi.org/10.1038/srep38138 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zhang, Enxiang
Yin, Shutao
Song, Xinhua
Fan, Lihong
Hu, Hongbo
Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress/GSK-3-mediated mitochondrial pathway
title Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress/GSK-3-mediated mitochondrial pathway
title_full Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress/GSK-3-mediated mitochondrial pathway
title_fullStr Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress/GSK-3-mediated mitochondrial pathway
title_full_unstemmed Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress/GSK-3-mediated mitochondrial pathway
title_short Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress/GSK-3-mediated mitochondrial pathway
title_sort glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of er stress/gsk-3-mediated mitochondrial pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5128870/
https://www.ncbi.nlm.nih.gov/pubmed/27901086
http://dx.doi.org/10.1038/srep38138
work_keys_str_mv AT zhangenxiang glycycoumarininhibitshepatocytelipoapoptosisthroughactivationofautophagyandinhibitionoferstressgsk3mediatedmitochondrialpathway
AT yinshutao glycycoumarininhibitshepatocytelipoapoptosisthroughactivationofautophagyandinhibitionoferstressgsk3mediatedmitochondrialpathway
AT songxinhua glycycoumarininhibitshepatocytelipoapoptosisthroughactivationofautophagyandinhibitionoferstressgsk3mediatedmitochondrialpathway
AT fanlihong glycycoumarininhibitshepatocytelipoapoptosisthroughactivationofautophagyandinhibitionoferstressgsk3mediatedmitochondrialpathway
AT huhongbo glycycoumarininhibitshepatocytelipoapoptosisthroughactivationofautophagyandinhibitionoferstressgsk3mediatedmitochondrialpathway