Saikosaponin D improves nonalcoholic fatty liver disease via gut microbiota-bile acid metabolism pathway

Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease worldwide. Bupleurum is widely used in the treatment of non-alcoholic fatty liver, and saikosaponin D (SSD) is one of the main active components of Bupleurum. The purpose of this study was to investigate the efficac...

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Main Authors: Lan Li, Shengye Yang, Xinyu Liang, Yameng Liu, Hualing Xu, Xiaozhen Guo, Cen Xie, Xiaojun Xu
Format: Article
Language:English
Published: Tsinghua University Press 2024-09-01
Series:Food Science and Human Wellness
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Online Access:https://www.sciopen.com/article/10.26599/FSHW.2022.9250218
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author Lan Li
Shengye Yang
Xinyu Liang
Yameng Liu
Hualing Xu
Xiaozhen Guo
Cen Xie
Xiaojun Xu
author_facet Lan Li
Shengye Yang
Xinyu Liang
Yameng Liu
Hualing Xu
Xiaozhen Guo
Cen Xie
Xiaojun Xu
author_sort Lan Li
collection DOAJ
description Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease worldwide. Bupleurum is widely used in the treatment of non-alcoholic fatty liver, and saikosaponin D (SSD) is one of the main active components of Bupleurum. The purpose of this study was to investigate the efficacy of SSD in the treatment of NAFLD and to explore the mechanism of SSD in the improvement of NAFLD based on “gut-liver axis”. Our results showed that SSD dose-dependently alleviated high fat diet-induced weight gain in mice, improved insulin sensitivity, and also reduced liver lipid accumulation and injury-related biomarkers aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Further exploration found that SSD inhibited the mRNA expression levels of farnesoid X receptor (Fxr), small heterodimer partner (Shp), recombinant fibroblast growth factor 15 (Fgf15) and apical sodium dependent bile acid transporter (Asbt) in the intestine, suggesting that SSD improved liver lipid metabolism by inhibiting intestinal FXR signaling. SSD can significantly reduce the gut microbiota associated with bile salt hydrolase (BSH) expression, such as Clostridium. Decreased BSH expression reduced the ratio of unconjugated to conjugated bile acids, thereby inhibiting the intestinal FXR. These data demonstrated that SSD ameliorated NAFLD potentially through the gut microbiota-bile acidintestinal FXR pathway and suggested that SSD is a promising therapeutic agent for the treatment of NAFLD.
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institution Kabale University
issn 2097-0765
2213-4530
language English
publishDate 2024-09-01
publisher Tsinghua University Press
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spelling doaj-art-85b6c0911d7547eb9bafcc40a965e8df2025-01-10T06:56:56ZengTsinghua University PressFood Science and Human Wellness2097-07652213-45302024-09-011352703271710.26599/FSHW.2022.9250218Saikosaponin D improves nonalcoholic fatty liver disease via gut microbiota-bile acid metabolism pathwayLan Li0Shengye Yang1Xinyu Liang2Yameng Liu3Hualing Xu4Xiaozhen Guo5Cen Xie6Xiaojun Xu7State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210029, ChinaState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210029, ChinaSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210029, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210029, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210029, ChinaState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210029, ChinaNon-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease worldwide. Bupleurum is widely used in the treatment of non-alcoholic fatty liver, and saikosaponin D (SSD) is one of the main active components of Bupleurum. The purpose of this study was to investigate the efficacy of SSD in the treatment of NAFLD and to explore the mechanism of SSD in the improvement of NAFLD based on “gut-liver axis”. Our results showed that SSD dose-dependently alleviated high fat diet-induced weight gain in mice, improved insulin sensitivity, and also reduced liver lipid accumulation and injury-related biomarkers aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Further exploration found that SSD inhibited the mRNA expression levels of farnesoid X receptor (Fxr), small heterodimer partner (Shp), recombinant fibroblast growth factor 15 (Fgf15) and apical sodium dependent bile acid transporter (Asbt) in the intestine, suggesting that SSD improved liver lipid metabolism by inhibiting intestinal FXR signaling. SSD can significantly reduce the gut microbiota associated with bile salt hydrolase (BSH) expression, such as Clostridium. Decreased BSH expression reduced the ratio of unconjugated to conjugated bile acids, thereby inhibiting the intestinal FXR. These data demonstrated that SSD ameliorated NAFLD potentially through the gut microbiota-bile acidintestinal FXR pathway and suggested that SSD is a promising therapeutic agent for the treatment of NAFLD.https://www.sciopen.com/article/10.26599/FSHW.2022.9250218saikosaponin d (ssd)non-alcoholic fatty liver diseasebile acidsgut microbiotafarnesoid x receptor
spellingShingle Lan Li
Shengye Yang
Xinyu Liang
Yameng Liu
Hualing Xu
Xiaozhen Guo
Cen Xie
Xiaojun Xu
Saikosaponin D improves nonalcoholic fatty liver disease via gut microbiota-bile acid metabolism pathway
Food Science and Human Wellness
saikosaponin d (ssd)
non-alcoholic fatty liver disease
bile acids
gut microbiota
farnesoid x receptor
title Saikosaponin D improves nonalcoholic fatty liver disease via gut microbiota-bile acid metabolism pathway
title_full Saikosaponin D improves nonalcoholic fatty liver disease via gut microbiota-bile acid metabolism pathway
title_fullStr Saikosaponin D improves nonalcoholic fatty liver disease via gut microbiota-bile acid metabolism pathway
title_full_unstemmed Saikosaponin D improves nonalcoholic fatty liver disease via gut microbiota-bile acid metabolism pathway
title_short Saikosaponin D improves nonalcoholic fatty liver disease via gut microbiota-bile acid metabolism pathway
title_sort saikosaponin d improves nonalcoholic fatty liver disease via gut microbiota bile acid metabolism pathway
topic saikosaponin d (ssd)
non-alcoholic fatty liver disease
bile acids
gut microbiota
farnesoid x receptor
url https://www.sciopen.com/article/10.26599/FSHW.2022.9250218
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