Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha-Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive Proteomic and Metabolomic Signatures

Background/Aims: Cholestasis is the major cause of the accumulation of bile acids and results in liver damage, fibrosis, and failure. A growing number of studies have shown that gentiopicroside is a promising prospect that may protect the liver. However, its therapeutic mechanism has not yet been cl...

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Main Authors: Han Han, Lili Xu, Kai Xiong, Tong  Zhang, Zhengtao Wang
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2018-09-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:https://www.karger.com/Article/FullText/493409
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author Han Han
Lili Xu
Kai Xiong
Tong  Zhang
Zhengtao Wang
author_facet Han Han
Lili Xu
Kai Xiong
Tong  Zhang
Zhengtao Wang
author_sort Han Han
collection DOAJ
description Background/Aims: Cholestasis is the major cause of the accumulation of bile acids and results in liver damage, fibrosis, and failure. A growing number of studies have shown that gentiopicroside is a promising prospect that may protect the liver. However, its therapeutic mechanism has not yet been clarified. This study aimed to explore the effect and mechanism of gentiopicroside in cholestasis induced by alpha-naphthylisothiocyanate. Methods: We performed isobaric tags for relative and absolute quantification-based quantitative proteomics and metabolomics using liquid chromatography quadruple time-of-fight mass spectrometry and identified the expression of 73 metabolites and 84 proteins associated with cholestasis-related dysfunctions in the metabolism of bile acids, fatty acids, and glycerophospholipids. Results: Integrated analyses of proteomic and metabonomic studies showed altered pathways in cholestasis-induced liver injury involving increased activity of farnesoid X receptor/retinoid X receptor, bile acid biosynthesis, and peroxisome proliferator-activated receptor-α/retinoid X receptor-α. Gentiopicroside could reverse these metabolite, protein, and blood biochemical indices, as well as alleviate liver damage. The progressive changes in the proteins and genes may be correlated with cholestasis and were confirmed by western blot and quantitative realtime polymerase chain reaction. Conclusion: Gentiopicroside could be used to protect the liver in the presence of cholestasis.
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spelling doaj.art-775d06c1054147de9cd0b9bbc3f963512022-12-21T19:07:49ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-09-014941304131910.1159/000493409493409Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha-Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive Proteomic and Metabolomic SignaturesHan HanLili XuKai XiongTong  ZhangZhengtao WangBackground/Aims: Cholestasis is the major cause of the accumulation of bile acids and results in liver damage, fibrosis, and failure. A growing number of studies have shown that gentiopicroside is a promising prospect that may protect the liver. However, its therapeutic mechanism has not yet been clarified. This study aimed to explore the effect and mechanism of gentiopicroside in cholestasis induced by alpha-naphthylisothiocyanate. Methods: We performed isobaric tags for relative and absolute quantification-based quantitative proteomics and metabolomics using liquid chromatography quadruple time-of-fight mass spectrometry and identified the expression of 73 metabolites and 84 proteins associated with cholestasis-related dysfunctions in the metabolism of bile acids, fatty acids, and glycerophospholipids. Results: Integrated analyses of proteomic and metabonomic studies showed altered pathways in cholestasis-induced liver injury involving increased activity of farnesoid X receptor/retinoid X receptor, bile acid biosynthesis, and peroxisome proliferator-activated receptor-α/retinoid X receptor-α. Gentiopicroside could reverse these metabolite, protein, and blood biochemical indices, as well as alleviate liver damage. The progressive changes in the proteins and genes may be correlated with cholestasis and were confirmed by western blot and quantitative realtime polymerase chain reaction. Conclusion: Gentiopicroside could be used to protect the liver in the presence of cholestasis.https://www.karger.com/Article/FullText/493409GentiopicrosideANIT-induced cholestasisProteomicsMetabolomics
spellingShingle Han Han
Lili Xu
Kai Xiong
Tong  Zhang
Zhengtao Wang
Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha-Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive Proteomic and Metabolomic Signatures
Cellular Physiology and Biochemistry
Gentiopicroside
ANIT-induced cholestasis
Proteomics
Metabolomics
title Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha-Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive Proteomic and Metabolomic Signatures
title_full Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha-Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive Proteomic and Metabolomic Signatures
title_fullStr Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha-Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive Proteomic and Metabolomic Signatures
title_full_unstemmed Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha-Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive Proteomic and Metabolomic Signatures
title_short Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha-Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive Proteomic and Metabolomic Signatures
title_sort exploration of hepatoprotective effect of gentiopicroside on alpha naphthylisothiocyanate induced cholestatic liver injury in rats by comprehensive proteomic and metabolomic signatures
topic Gentiopicroside
ANIT-induced cholestasis
Proteomics
Metabolomics
url https://www.karger.com/Article/FullText/493409
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