Naringenin Prevents Oxidative Stress and Inflammation in LPS-Induced Liver Injury through the Regulation of LncRNA-mRNA in Male Mice

Inflammation accompanies hepatic dysfunction resulting from tissue oxidative damage. Naringenin (Nar), a natural flavanone, has known antioxidant and anti-inflammatory activities, but its mechanism of action in the regulation of liver dysfunction requires further investigation. In this study, the role of naringenin in lipopolysaccharide (LPS)-induced hepatic oxidative stress and inflammation was explored, as well as its mechanism by transcriptome sequencing. The results indicated that compared with the LPS group, Nar treatment caused a significant increase in the mRNA levels of antioxidant factors glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM), yet the expression of related inflammatory factors (MCP1, TNF alpha, IL-1 beta and IL-6) showed less of an increase. RNA sequencing identified 36 differentially expressed lncRNAs and 603 differentially expressed mRNAs. KEGG enrichment analysis indicated that oxidative stress and inflammation pathways are meticulously linked with naringenin treatment. The Co-lncRNA-mRNA network was also constructed. Tissue expression profiles showed that lncRNA played a higher role in the liver. Subsequently, expression levels of inflammatory factors indicated that lncRNAs and target mRNAs were significantly reduced after naringenin treatment in mouse liver AML12 cells and obese mouse. These results suggest that naringenin helps to prevent liver dysfunction through the regulation of lncRNA-mRNA axis to reduce oxidative stress and inflammatory factors.

Automated summary

Inflammation and oxidative damage can lead to hepatic dysfunction. Naringenin, a natural flavanone, has antioxidant and anti-inflammatory properties, but its role in regulating liver dysfunction is not well understood. This study investigated the effect of naringenin on lipopolysaccharide-induced oxidative stress and inflammation in the liver, as well as its mechanism of action. The results showed that naringenin increased the mRNA levels of antioxidant factors and reduced the expression of inflammatory factors. Transcriptome sequencing identified differentially expressed lncRNAs and mRNAs, and KEGG enrichment analysis revealed the involvement of oxidative stress and inflammation pathways. Tissue expression profiles and cell experiments further confirmed the role of lncRNAs and target mRNAs in the regulation of liver dysfunction by naringenin.