Gut Microbiota and Bile Acid Metabolism in the Mechanism of Ginsenoside Re Against Nonalcoholic Fatty Liver Disease

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Autores principales: Yanfang Zheng, Jiaying Chen, Ying Zhang, Huaying Guan, Shan Deng, Dennis Chang, Yitao Wang, JinJian Lu, Xian Zhou, Qin Xie, Jianyuan Song, Mingqing Huang
Formato: Artículo Open Access
Publicado: Wiley 2025
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author Yanfang Zheng
Jiaying Chen
Ying Zhang
Huaying Guan
Shan Deng
Dennis Chang
Yitao Wang
JinJian Lu
Xian Zhou
Qin Xie
Jianyuan Song
Mingqing Huang
author_facet Yanfang Zheng
Jiaying Chen
Ying Zhang
Huaying Guan
Shan Deng
Dennis Chang
Yitao Wang
JinJian Lu
Xian Zhou
Qin Xie
Jianyuan Song
Mingqing Huang
Yanfang Zheng
Jiaying Chen
Ying Zhang
Huaying Guan
Shan Deng
Dennis Chang
Yitao Wang
JinJian Lu
Xian Zhou
Qin Xie
Jianyuan Song
Mingqing Huang
collection Wiley Open Access
contents Gut Microbiota and Bile Acid Metabolism in the Mechanism of Ginsenoside Re Against Nonalcoholic Fatty Liver Disease Yanfang Zheng Jiaying Chen Ying Zhang Huaying Guan Shan Deng Dennis Chang Yitao Wang JinJian Lu Xian Zhou Qin Xie Jianyuan Song Mingqing Huang Phytotherapy Research ABSTRACTGut microbiota and bile acid metabolism play crucial roles in the progression of nonalcoholic fatty liver disease (NAFLD). Early evidence demonstrates that Ginsenoside Re (Re) possesses pharmacological effects on NAFLD, but its mechanisms of action are not well understood. This study aimed to investigate the hepatic protective effects of Re in NAFLD and elucidate relevant mechanisms. The effects of Re treatments (10, 20, or 40 mg/kg) against high‐fat diet‐induced NAFLD were initially tested on male C57BL/6 mice. Then, a separate mouse group received Re with or without antibiotics to confirm the regulatory role of microbiota in the effect of Re. Finally, another group of mice received fecal microbiota transplantation (FMT) from the initial experiment of NAFLD mice to further investigate the mechanistic role of gut microbiota. Re significantly improved liver function by reducing hepatic lipid accumulation, injury and hepatocyte steatosis, and inflammation. The liver protection was mediated by the regulation of gut microbiota as evidenced by restored intestinal barrier integrity, normalized Firmicutes/Bacteroidota ratio, enhanced abundances of Adlercreutzia equolifaciens , and reduced Faecalibaculum rodentium. Following that, Re reduced total and primary bile acids and downregulated bile acid synthesis genes and proteins such as farnesoid X receptor and cytochrome P450 family 7 subfamily A member 1. The co‐administration of antibiotic cocktail counteracted the effect of Re against NAFLD. Further, the results obtained from the FMT animal study confirmed that Re's liver protective effects were at least partly driven by the regulation of gut microbiota. Re modulated bile salt hydrolase‐related microbial genera to alter bile acid synthesis pathways, thereby inhibiting NAFLD progression. 10.1002/ptr.8474 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/ptr.8474
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id wiley_oa_10_1002_ptr_8474
institution Wiley Open Access
license_str_mv http://onlinelibrary.wiley.com/termsAndConditions#vor
publishDate 2025
publisher Wiley
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spellingShingle Gut Microbiota and Bile Acid Metabolism in the Mechanism of Ginsenoside Re Against Nonalcoholic Fatty Liver Disease
Yanfang Zheng
Jiaying Chen
Ying Zhang
Huaying Guan
Shan Deng
Dennis Chang
Yitao Wang
JinJian Lu
Xian Zhou
Qin Xie
Jianyuan Song
Mingqing Huang
Phytotherapy Research
Gut Microbiota and Bile Acid Metabolism in the Mechanism of Ginsenoside Re Against Nonalcoholic Fatty Liver Disease Yanfang Zheng Jiaying Chen Ying Zhang Huaying Guan Shan Deng Dennis Chang Yitao Wang JinJian Lu Xian Zhou Qin Xie Jianyuan Song Mingqing Huang Phytotherapy Research ABSTRACTGut microbiota and bile acid metabolism play crucial roles in the progression of nonalcoholic fatty liver disease (NAFLD). Early evidence demonstrates that Ginsenoside Re (Re) possesses pharmacological effects on NAFLD, but its mechanisms of action are not well understood. This study aimed to investigate the hepatic protective effects of Re in NAFLD and elucidate relevant mechanisms. The effects of Re treatments (10, 20, or 40 mg/kg) against high‐fat diet‐induced NAFLD were initially tested on male C57BL/6 mice. Then, a separate mouse group received Re with or without antibiotics to confirm the regulatory role of microbiota in the effect of Re. Finally, another group of mice received fecal microbiota transplantation (FMT) from the initial experiment of NAFLD mice to further investigate the mechanistic role of gut microbiota. Re significantly improved liver function by reducing hepatic lipid accumulation, injury and hepatocyte steatosis, and inflammation. The liver protection was mediated by the regulation of gut microbiota as evidenced by restored intestinal barrier integrity, normalized Firmicutes/Bacteroidota ratio, enhanced abundances of Adlercreutzia equolifaciens , and reduced Faecalibaculum rodentium. Following that, Re reduced total and primary bile acids and downregulated bile acid synthesis genes and proteins such as farnesoid X receptor and cytochrome P450 family 7 subfamily A member 1. The co‐administration of antibiotic cocktail counteracted the effect of Re against NAFLD. Further, the results obtained from the FMT animal study confirmed that Re's liver protective effects were at least partly driven by the regulation of gut microbiota. Re modulated bile salt hydrolase‐related microbial genera to alter bile acid synthesis pathways, thereby inhibiting NAFLD progression. 10.1002/ptr.8474 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Gut Microbiota and Bile Acid Metabolism in the Mechanism of Ginsenoside Re Against Nonalcoholic Fatty Liver Disease
topic Phytotherapy Research
url https://onlinelibrary.wiley.com/doi/10.1002/ptr.8474