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

被引:127
作者
Guo, Weiling [1 ,2 ]
Xiang, Qunran [1 ,2 ]
Mao, Bingyong [1 ,2 ]
Tang, Xin [1 ,2 ]
Cui, Shumao [1 ,2 ]
Li, Xiangfei [4 ]
Zhao, Jianxin [1 ,2 ]
Zhang, Hao [1 ,2 ,3 ]
Chen, Wei [1 ,2 ,3 ]
机构
[1] Jiangnan Univ, State Key Lab Food Sci & Technol, Wuxi 214122, Jiangsu, Peoples R China
[2] Jiangnan Univ, Sch Food Sci & Technol, Wuxi 214122, Jiangsu, Peoples R China
[3] Jiangnan Univ, Natl Engn Res Ctr Funct Food, Wuxi 214122, Jiangsu, Peoples R China
[4] Nanjing Univ Finance & Econ, Coll Food Sci & Engn, Nanjing 210023, Peoples R China
基金
中国国家自然科学基金;
关键词
Inosine; acute liver damage; inflammation; intestinal microbiota; mRNA expression; NF-KAPPA-B; OXIDATIVE STRESS; INDUCED HEPATOTOXICITY; D-GALACTOSAMINE; GUT; CELLS; ACID; MECHANISM; INHIBITION; EXPRESSION;
D O I
10.1021/acs.jafc.1c01781
中图分类号
S [农业科学];
学科分类号
09 ;
摘要
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-kappa B, iNOS, COX2, AMPK, Nfr2, and I kappa B-alpha 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-kappa B signaling pathway.
引用
收藏
页码:7619 / 7628
页数:10
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