Protective Effects of Microbiome-Derived Inosine on Lipopolysaccharide-Induced Acute Liver Damage and Inflammation in Mice via Mediating the TLR4/NF-κB Pathway

Weiling Guo; Qunran Xiang; Bingyong Mao; Xin Tang; Shumao Cui; Xiangfei Li; Jianxin Zhao; Hao Zhang; Wei Chen

doi:10.1021/acs.jafc.1c01781

Protective Effects of Microbiome-Derived Inosine on Lipopolysaccharide-Induced Acute Liver Damage and Inflammation in Mice via Mediating the TLR4/NF-κB Pathway

J Agric Food Chem. 2021 Jul 14;69(27):7619-7628. doi: 10.1021/acs.jafc.1c01781. Epub 2021 Jun 22.

Authors

Weiling Guo^{1

2}, Qunran Xiang^{1

2}, Bingyong Mao^{1

2}, Xin Tang^{1

2}, Shumao Cui^{1

2}, Xiangfei Li³, Jianxin Zhao^{1

2}, Hao Zhang^{1

2

4}, Wei Chen^{1

2

4}

Affiliations

¹ State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
² School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
³ College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China.
⁴ National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China.

PMID: 34156842
DOI: 10.1021/acs.jafc.1c01781

Abstract

This research assessed the anti-inflammatory and hepatoprotective properties of inosine and the associated mechanism. Inosine pretreatment significantly reduced the secretion of several inflammatory factors and serum alanine transaminase (ALT) and aspartate amino transferase (AST) levels in a dose-dependent manner compared with the lipopolysaccharide (LPS) group. In LPS-treated mice, inosine pretreatment significantly reduced the ALT and malondialdehyde (MDA) concentration and significantly elevated the antioxidant enzyme activity. Furthermore, inosine pretreatment significantly altered the relative abundance of the genera, Bifidobacterium, Lachnospiraceae UCG-006, and Muribaculum. Correlation analysis showed that Bifidobacterium and Lachnospiraceae UCG-006 were positively related to the cecal short-chain fatty acids but negatively related to the serum IL-6 and hepatic AST and ALT levels. Notably, inosine pretreatment significantly modulated the hepatic TLR4, MYD88, NF-κB, iNOS, COX2, AMPK, Nfr2, and IκB-α expression. These results suggested that inosine pretreatment alters the intestinal microbiota structure and improves LPS-induced acute liver damage and inflammation through modulating the TLR4/NF-κB signaling pathway.

Keywords: Inosine; acute liver damage; inflammation; intestinal microbiota; mRNA expression.

MeSH terms

Animals
Chemical and Drug Induced Liver Injury* / drug therapy
Chemical and Drug Induced Liver Injury* / genetics
Inflammation / drug therapy
Inosine
Lipopolysaccharides / adverse effects
Liver
Mice
Microbiota*
NF-kappa B / genetics
Toll-Like Receptor 4 / genetics

Substances

Lipopolysaccharides
NF-kappa B
Tlr4 protein, mouse
Toll-Like Receptor 4
Inosine