Isoliquiritigenin-mediated miR-23a-3p inhibition activates PGC-1a to alleviate alcoholic liver injury

Background: Alcoholic liver disease (ALD), one of the most prevalent forms of liver disease, has received wide attention worldwide. However, limited efficient and appropriate therapeutic agents were responded to ALD. Isoliquiritigenin (ISL), a flavonoid isolated from liquorice, possesses multiple pharmacological activities. Purpose: The current study investigated the hepatoprotective effect of ISL against ALD and further elucidate the involvement of miR-23a-3p/peroxisome proliferative activated receptor-gamma coactivator 1 alpha (PGC-1 alpha) in vivo and in vitro experiments. Study design and Methods: In the study, H&E and Oil Red O staining were employed to detect liver histopathological changes and the accumulation of lipid droplets. Quantitative real-time PCR, bioinformatics, luciferase assay, immunofluorescence staining, reactive oxygen species (ROS), Western blot, and siRNA were used to further explore the mechanism of ISL protection. Results: ISL significantly reduced the liver-to-body weight ratios and biochemical index. The staining results showed that ISL remarkedly ameliorated the histopathological changes in the liver. Furthermore, ISL promoted fatty acid metabolism via induction in the expression of PGC-1 alpha-target genes PPAR alpha, CPT1 alpha, and ACADs, and inhibited the ROS, TNF-alpha, IL-1 beta, and IL-6 expression. Bioinformatics and Luciferase assay analysis confirmed that miR-23a-3p might bind to PGC-1 alpha mRNA in ALD. Significantly, the expression of miR-23a-3p was increased in the ALD, which was significantly decreased by ISL. In addition, the miR-23a-3p inhibitor also promoted lipid metabolism in ALD via PGC-1 alpha activation. Conclusions: We first demonstrated that ISL could alleviate ALD, and further verified that ISL exerted protective effects through modulating miR-23a-3p/PGC-1 alpha-mediated lipid metabolism in vivo and in vitro.

Automated summary

Isoliquiritigenin (ISL) demonstrates hepatoprotective effects against alcoholic liver disease (ALD) by promoting fatty acid metabolism, inhibiting oxidative stress and inflammation, and ameliorating liver histopathological changes.