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Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation

Cholestasis is a kind of stressful syndrome along with liver toxicity, which has been demonstrated to be related to fibrosis, cirrhosis, even cholangiocellular or hepatocellular carcinomas. Cholestasis usually caused by the dysregulated metabolism of bile acids that possess high cellular toxicity an...

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Autores principales: Wu, Peijie, Qiao, Ling, Yu, Han, Ming, Hui, Liu, Chao, Wu, Wenjun, Li, Baixue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675020/
https://www.ncbi.nlm.nih.gov/pubmed/34926449
http://dx.doi.org/10.3389/fcell.2021.758632
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author Wu, Peijie
Qiao, Ling
Yu, Han
Ming, Hui
Liu, Chao
Wu, Wenjun
Li, Baixue
author_facet Wu, Peijie
Qiao, Ling
Yu, Han
Ming, Hui
Liu, Chao
Wu, Wenjun
Li, Baixue
author_sort Wu, Peijie
collection PubMed
description Cholestasis is a kind of stressful syndrome along with liver toxicity, which has been demonstrated to be related to fibrosis, cirrhosis, even cholangiocellular or hepatocellular carcinomas. Cholestasis usually caused by the dysregulated metabolism of bile acids that possess high cellular toxicity and synthesized by cholesterol in the liver to undergo enterohepatic circulation. In cholestasis, the accumulation of bile acids in the liver causes biliary and hepatocyte injury, oxidative stress, and inflammation. The farnesoid X receptor (FXR) is regarded as a bile acid–activated receptor that regulates a network of genes involved in bile acid metabolism, providing a new therapeutic target to treat cholestatic diseases. Arbutin is a glycosylated hydroquinone isolated from medicinal plants in the genus Arctostaphylos, which has a variety of potentially pharmacological properties, such as anti-inflammatory, antihyperlipidemic, antiviral, antihyperglycemic, and antioxidant activity. However, the mechanistic contributions of arbutin to alleviate liver injury of cholestasis, especially its role on bile acid homeostasis via nuclear receptors, have not been fully elucidated. In this study, we demonstrate that arbutin has a protective effect on α-naphthylisothiocyanate–induced cholestasis via upregulation of the levels of FXR and downstream enzymes associated with bile acid homeostasis such as Bsep, Ntcp, and Sult2a1, as well as Ugt1a1. Furthermore, the regulation of these functional proteins related to bile acid homeostasis by arbutin could be alleviated by FXR silencing in L-02 cells. In conclusion, a protective effect could be supported by arbutin to alleviate ANIT-induced cholestatic liver toxicity, which was partly through the FXR pathway, suggesting arbutin may be a potential chemical molecule for the cholestatic disease.
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spelling pubmed-86750202021-12-17 Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation Wu, Peijie Qiao, Ling Yu, Han Ming, Hui Liu, Chao Wu, Wenjun Li, Baixue Front Cell Dev Biol Cell and Developmental Biology Cholestasis is a kind of stressful syndrome along with liver toxicity, which has been demonstrated to be related to fibrosis, cirrhosis, even cholangiocellular or hepatocellular carcinomas. Cholestasis usually caused by the dysregulated metabolism of bile acids that possess high cellular toxicity and synthesized by cholesterol in the liver to undergo enterohepatic circulation. In cholestasis, the accumulation of bile acids in the liver causes biliary and hepatocyte injury, oxidative stress, and inflammation. The farnesoid X receptor (FXR) is regarded as a bile acid–activated receptor that regulates a network of genes involved in bile acid metabolism, providing a new therapeutic target to treat cholestatic diseases. Arbutin is a glycosylated hydroquinone isolated from medicinal plants in the genus Arctostaphylos, which has a variety of potentially pharmacological properties, such as anti-inflammatory, antihyperlipidemic, antiviral, antihyperglycemic, and antioxidant activity. However, the mechanistic contributions of arbutin to alleviate liver injury of cholestasis, especially its role on bile acid homeostasis via nuclear receptors, have not been fully elucidated. In this study, we demonstrate that arbutin has a protective effect on α-naphthylisothiocyanate–induced cholestasis via upregulation of the levels of FXR and downstream enzymes associated with bile acid homeostasis such as Bsep, Ntcp, and Sult2a1, as well as Ugt1a1. Furthermore, the regulation of these functional proteins related to bile acid homeostasis by arbutin could be alleviated by FXR silencing in L-02 cells. In conclusion, a protective effect could be supported by arbutin to alleviate ANIT-induced cholestatic liver toxicity, which was partly through the FXR pathway, suggesting arbutin may be a potential chemical molecule for the cholestatic disease. Frontiers Media S.A. 2021-12-02 /pmc/articles/PMC8675020/ /pubmed/34926449 http://dx.doi.org/10.3389/fcell.2021.758632 Text en Copyright © 2021 Wu, Qiao, Yu, Ming, Liu, Wu and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Wu, Peijie
Qiao, Ling
Yu, Han
Ming, Hui
Liu, Chao
Wu, Wenjun
Li, Baixue
Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation
title Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation
title_full Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation
title_fullStr Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation
title_full_unstemmed Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation
title_short Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation
title_sort arbutin alleviates the liver injury of α-naphthylisothiocyanate-induced cholestasis through farnesoid x receptor activation
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675020/
https://www.ncbi.nlm.nih.gov/pubmed/34926449
http://dx.doi.org/10.3389/fcell.2021.758632
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