Forsythiaside A alleviated carbon tetrachloride-induced liver fibrosis by modulating gut microbiota composition to increase short-chain fatty acids and restoring bile acids metabolism disorder

Liver fibrosis is a chronic and progressive disease with complex pathogenesis related to bile acids (BAs) and gut microbiota. Forsythiaside A (FTA), isolated from the traditional Chinese medicine Forsythiae Fructus (Lian Qiao), is a natural hepatoprotective agent. The purpose of this study was to in...

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Published inBiomedicine & pharmacotherapy Vol. 151; p. 113185
Main Authors Fu, Ke, Ma, Cheng, Wang, Cheng, Zhou, Honglin, Gong, Lihong, Zhang, Yafang, Li, Yunxia
Format Journal Article
LanguageEnglish
Published France Elsevier Masson SAS 01.07.2022
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Abstract Liver fibrosis is a chronic and progressive disease with complex pathogenesis related to bile acids (BAs) and gut microbiota. Forsythiaside A (FTA), isolated from the traditional Chinese medicine Forsythiae Fructus (Lian Qiao), is a natural hepatoprotective agent. The purpose of this study was to investigate the protective effect of FTA on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Liver fibrosis was induced in mice by intraperitoneal injection of 2 mL/kg CCl4 three times a week for 4 weeks. FTA attenuated CCl4-induced liver fibrosis in mice, which was proved by the results of Masson and Sirius red staining, liver hydroxyproline, hyaluronic acid, laminin, type III procollagen, and type IV collagen assays. FTA inhibited hepatic stellate cell activation, and reduced hepatic inflammation and oxidative stress in mice treated with CCl4. What’s more, FTA ameliorated CCl4-induced gut dysbiosis, maintained intestinal barrier function, increased the production of short-chain fatty acids (SCFAs), and improved endotoxemia, as manifested by decreased serum lipopolysaccharide levels and increased expression of ileal tight junction proteins. Besides, FTA can modulate the genes related to bile acid metabolism to alter the distribution of fecal BAs in fibrotic mice. In a word, FTA can improve liver fibrosis by inhibiting inflammation and oxidative stress, regulating gut microbiota and BA metabolism, and increasing the content of SCFAs. The results of this study provided an important reference for the study on the mechanisms by which natural products prevent liver fibrosis. [Display omitted] •FTA attenuated CCl4-induced liver inflammation, oxidative stress, and fibrosis.•FTA increased the content of SCFAs by modulating the composition of gut microbiota.•FTA protected the intestinal barrier and reduce serum endotoxin and inflammation.•FTA altered the fecal BAs profile to improve liver fibrosis.
AbstractList Liver fibrosis is a chronic and progressive disease with complex pathogenesis related to bile acids (BAs) and gut microbiota. Forsythiaside A (FTA), isolated from the traditional Chinese medicine Forsythiae Fructus (Lian Qiao), is a natural hepatoprotective agent. The purpose of this study was to investigate the protective effect of FTA on carbon tetrachloride (CCl )-induced liver fibrosis in mice. Liver fibrosis was induced in mice by intraperitoneal injection of 2 mL/kg CCl three times a week for 4 weeks. FTA attenuated CCl -induced liver fibrosis in mice, which was proved by the results of Masson and Sirius red staining, liver hydroxyproline, hyaluronic acid, laminin, type III procollagen, and type IV collagen assays. FTA inhibited hepatic stellate cell activation, and reduced hepatic inflammation and oxidative stress in mice treated with CCl . What's more, FTA ameliorated CCl -induced gut dysbiosis, maintained intestinal barrier function, increased the production of short-chain fatty acids (SCFAs), and improved endotoxemia, as manifested by decreased serum lipopolysaccharide levels and increased expression of ileal tight junction proteins. Besides, FTA can modulate the genes related to bile acid metabolism to alter the distribution of fecal BAs in fibrotic mice. In a word, FTA can improve liver fibrosis by inhibiting inflammation and oxidative stress, regulating gut microbiota and BA metabolism, and increasing the content of SCFAs. The results of this study provided an important reference for the study on the mechanisms by which natural products prevent liver fibrosis.
Liver fibrosis is a chronic and progressive disease with complex pathogenesis related to bile acids (BAs) and gut microbiota. Forsythiaside A (FTA), isolated from the traditional Chinese medicine Forsythiae Fructus (Lian Qiao), is a natural hepatoprotective agent. The purpose of this study was to investigate the protective effect of FTA on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Liver fibrosis was induced in mice by intraperitoneal injection of 2 mL/kg CCl4 three times a week for 4 weeks. FTA attenuated CCl4-induced liver fibrosis in mice, which was proved by the results of Masson and Sirius red staining, liver hydroxyproline, hyaluronic acid, laminin, type III procollagen, and type IV collagen assays. FTA inhibited hepatic stellate cell activation, and reduced hepatic inflammation and oxidative stress in mice treated with CCl4. What’s more, FTA ameliorated CCl4-induced gut dysbiosis, maintained intestinal barrier function, increased the production of short-chain fatty acids (SCFAs), and improved endotoxemia, as manifested by decreased serum lipopolysaccharide levels and increased expression of ileal tight junction proteins. Besides, FTA can modulate the genes related to bile acid metabolism to alter the distribution of fecal BAs in fibrotic mice. In a word, FTA can improve liver fibrosis by inhibiting inflammation and oxidative stress, regulating gut microbiota and BA metabolism, and increasing the content of SCFAs. The results of this study provided an important reference for the study on the mechanisms by which natural products prevent liver fibrosis. [Display omitted] •FTA attenuated CCl4-induced liver inflammation, oxidative stress, and fibrosis.•FTA increased the content of SCFAs by modulating the composition of gut microbiota.•FTA protected the intestinal barrier and reduce serum endotoxin and inflammation.•FTA altered the fecal BAs profile to improve liver fibrosis.
ArticleNumber 113185
Author Li, Yunxia
Ma, Cheng
Fu, Ke
Zhang, Yafang
Wang, Cheng
Gong, Lihong
Zhou, Honglin
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Keywords Gut microbiota
LN
ALP
PC-III
ALT
MDA
Liver fibrosis
α-SMA
OTU
BAs
NTCP
Col-IV
HSC
qPCR
SHP
Forsythiaside A
Short-chain fatty acids
IL
BSEP
Bile acids
FTA
CCl4
CAT
ROS
FF
FXR
LDA
CYP7A1
LPS
RDA
Nrf2
MIP-1α
GSH
HYP
AST
GSH-Px
MRP2
γ-GT
SOD
Inflammation
ECM
LEfSe
LRH-1
TNF-α
OATP-1
SCFAs
HA
FGFR4
HE
Language English
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Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
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Snippet Liver fibrosis is a chronic and progressive disease with complex pathogenesis related to bile acids (BAs) and gut microbiota. Forsythiaside A (FTA), isolated...
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SubjectTerms Bile acids
Forsythiaside A
Gut microbiota
Inflammation
Liver fibrosis
Short-chain fatty acids
Title Forsythiaside A alleviated carbon tetrachloride-induced liver fibrosis by modulating gut microbiota composition to increase short-chain fatty acids and restoring bile acids metabolism disorder
URI https://dx.doi.org/10.1016/j.biopha.2022.113185
https://www.ncbi.nlm.nih.gov/pubmed/35623173
https://search.proquest.com/docview/2671270778
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