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Silymarin Ameliorates Metabolic Dysfunction Associated with Diet-Induced Obesity via Activation of Farnesyl X Receptor

Background and purpose: Silymarin, a standardized extract of the milk thistle seeds, has been widely used to treat chronic hepatitis, cirrhosis, and other types of toxic liver damage. Despite increasing studies on the action of silymarin and its major active constituent, silybin in their therapeutic...

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Autores principales: Gu, Ming, Zhao, Ping, Huang, Jinwen, Zhao, Yuanyuan, Wang, Yahui, Li, Yin, Li, Yifei, Fan, Shengjie, Ma, Yue-Ming, Tong, Qingchun, Yang, Li, Ji, Guang, Huang, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039206/
https://www.ncbi.nlm.nih.gov/pubmed/27733832
http://dx.doi.org/10.3389/fphar.2016.00345
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author Gu, Ming
Zhao, Ping
Huang, Jinwen
Zhao, Yuanyuan
Wang, Yahui
Li, Yin
Li, Yifei
Fan, Shengjie
Ma, Yue-Ming
Tong, Qingchun
Yang, Li
Ji, Guang
Huang, Cheng
author_facet Gu, Ming
Zhao, Ping
Huang, Jinwen
Zhao, Yuanyuan
Wang, Yahui
Li, Yin
Li, Yifei
Fan, Shengjie
Ma, Yue-Ming
Tong, Qingchun
Yang, Li
Ji, Guang
Huang, Cheng
author_sort Gu, Ming
collection PubMed
description Background and purpose: Silymarin, a standardized extract of the milk thistle seeds, has been widely used to treat chronic hepatitis, cirrhosis, and other types of toxic liver damage. Despite increasing studies on the action of silymarin and its major active constituent, silybin in their therapeutic properties against insulin resistance, diabetes and hyperlipidaemia in vitro and in vivo, the mechanism underlying silymarin action remains unclear. Experimental approach: C57BL/6 mice were fed high-fat diet (HFD) for 3 months to induce obesity, insulin resistance, hyperlipidaemia, and fatty liver. These mice were then continuously treated with HFD alone or mixed with silymarin at 40 mg/100 g for additional 6 weeks. Biochemical analysis was used to test the serum lipid and bile acid profiles. Farnesyl X receptor (FXR) and nuclear factor kappa B (NF-κB) transactivities were analyzed in liver using a gene reporter assay based on quantitative RT-PCR. Key results: Silymarin treatment ameliorated insulin resistance, dyslipidaemia and inflammation, and reconstituted the bile acid pool in liver of diet-induced obesity. Associated with this, silybin and silymarin enhanced FXR transactivity. Consistently, in HepG2 cells, silybin inhibited NF-κB signaling, which was enhanced by FXR activation. Conclusion and implications: Our results suggest that silybin is an effective component of silymarin for treating metabolic syndrome by stimulating FXR signaling.
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spelling pubmed-50392062016-10-12 Silymarin Ameliorates Metabolic Dysfunction Associated with Diet-Induced Obesity via Activation of Farnesyl X Receptor Gu, Ming Zhao, Ping Huang, Jinwen Zhao, Yuanyuan Wang, Yahui Li, Yin Li, Yifei Fan, Shengjie Ma, Yue-Ming Tong, Qingchun Yang, Li Ji, Guang Huang, Cheng Front Pharmacol Pharmacology Background and purpose: Silymarin, a standardized extract of the milk thistle seeds, has been widely used to treat chronic hepatitis, cirrhosis, and other types of toxic liver damage. Despite increasing studies on the action of silymarin and its major active constituent, silybin in their therapeutic properties against insulin resistance, diabetes and hyperlipidaemia in vitro and in vivo, the mechanism underlying silymarin action remains unclear. Experimental approach: C57BL/6 mice were fed high-fat diet (HFD) for 3 months to induce obesity, insulin resistance, hyperlipidaemia, and fatty liver. These mice were then continuously treated with HFD alone or mixed with silymarin at 40 mg/100 g for additional 6 weeks. Biochemical analysis was used to test the serum lipid and bile acid profiles. Farnesyl X receptor (FXR) and nuclear factor kappa B (NF-κB) transactivities were analyzed in liver using a gene reporter assay based on quantitative RT-PCR. Key results: Silymarin treatment ameliorated insulin resistance, dyslipidaemia and inflammation, and reconstituted the bile acid pool in liver of diet-induced obesity. Associated with this, silybin and silymarin enhanced FXR transactivity. Consistently, in HepG2 cells, silybin inhibited NF-κB signaling, which was enhanced by FXR activation. Conclusion and implications: Our results suggest that silybin is an effective component of silymarin for treating metabolic syndrome by stimulating FXR signaling. Frontiers Media S.A. 2016-09-28 /pmc/articles/PMC5039206/ /pubmed/27733832 http://dx.doi.org/10.3389/fphar.2016.00345 Text en Copyright © 2016 Gu, Zhao, Huang, Zhao, Wang, Li, Li, Fan, Ma, Tong, Yang, Ji and Huang. http://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) or licensor 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 Pharmacology
Gu, Ming
Zhao, Ping
Huang, Jinwen
Zhao, Yuanyuan
Wang, Yahui
Li, Yin
Li, Yifei
Fan, Shengjie
Ma, Yue-Ming
Tong, Qingchun
Yang, Li
Ji, Guang
Huang, Cheng
Silymarin Ameliorates Metabolic Dysfunction Associated with Diet-Induced Obesity via Activation of Farnesyl X Receptor
title Silymarin Ameliorates Metabolic Dysfunction Associated with Diet-Induced Obesity via Activation of Farnesyl X Receptor
title_full Silymarin Ameliorates Metabolic Dysfunction Associated with Diet-Induced Obesity via Activation of Farnesyl X Receptor
title_fullStr Silymarin Ameliorates Metabolic Dysfunction Associated with Diet-Induced Obesity via Activation of Farnesyl X Receptor
title_full_unstemmed Silymarin Ameliorates Metabolic Dysfunction Associated with Diet-Induced Obesity via Activation of Farnesyl X Receptor
title_short Silymarin Ameliorates Metabolic Dysfunction Associated with Diet-Induced Obesity via Activation of Farnesyl X Receptor
title_sort silymarin ameliorates metabolic dysfunction associated with diet-induced obesity via activation of farnesyl x receptor
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039206/
https://www.ncbi.nlm.nih.gov/pubmed/27733832
http://dx.doi.org/10.3389/fphar.2016.00345
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