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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Tsinghua University Press
2024-09-01
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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. |
format | Article |
id | doaj-art-85b6c0911d7547eb9bafcc40a965e8df |
institution | Kabale University |
issn | 2097-0765 2213-4530 |
language | English |
publishDate | 2024-09-01 |
publisher | Tsinghua University Press |
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series | Food Science and Human Wellness |
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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