Glycyrrhizic acid prevents alcohol-induced hepatocyte injury by inhibiting PPAR-gamma DNA methylation

Xuebin Y, Jiang P, Tang Y, Bi W, Yan Q and Ling Li

Published on: 2023-10-28

Abstract

Objective

To investigate the effect and mechanism of glycyrrhizic acid in alcohol-induced hepatocyte injury.

Methods

Alcohol was applied to induce hepatocyte injury. The viability of rat hepatocyte BRL-3A cells was measured using cell counting kit 8. Aminotransferase and aspartate aminotransferase levels were used to investigate hepatocyte injury. Lipid droplet accumulation was evaluated through oil-red staining. The protein expression levels of DNMT1, PPAR-γ, TLR4, p-P65/P65, IL-1β, bcl-2, bax, and caspase-3in the hepatocyte were assessed via western blot assay. In molecular docking studies, discovery studio software was used to calculate the binding energies of GA with PPAR-γ and to visualize the simulation results. PPAR-γ gene pyrosequencing was applied to assess the methylation level of PPAR-γ.

Results

GA markedly decreased the elevation of ALT and AST levels and lipid droplet accumulation. GA also significantly attenuated alcohol-induced apoptosis and toxicity by reducing the levels of Bax/Bcl-2 and caspase-3. Mechanistically, GA upregulated PPAR-γ expression by decreasing DNA methylation levels of the PPAR-γ promoter and reduced the protein expression levels of DNMT1, TLR4, p-P65/P65, and IL-1β.

Conclusion

In conclusion, our study shows that GA upregulated the expression of PPAR-γ by decreasing DNA demethylation levels of the PPAR-γ promoter, thereby negatively regulating the TRL4/NF-κB signaling pathway, and thus, leading to anti-inflammatory and antiapoptotic effects in a cellular model of hepatocyte injury.