Glycyrrhizin, silymarin, and ursodeoxycholic acid regulate a common hepatoprotective pathway in HepG2 cells. Homo sapiens

Background: Glycyrrhizin, silymarin, and ursodeoxycholic acid are widely used hepatoprotectants for the treatment of liver disorders, such as hepatitis C virus infection, primary biliary cirrhosis, and hepatocellular carcinoma. Hypothesis/Purpose: However, few studies have evaluated the effects of these compounds on gene expression. Methods: Here, we used an oligonucleotide microarray approach to study the gene expression profile in human hepatoma cells treated with 25 μM of hepatoprotective agents. Results: Among a total of 30,968 genes, 252 genes were commonly regulated by all compounds. These compounds affected the expressions of genes involved in different biological pathways, such as neurotransmission and glucose and lipid metabolism. Genes involved in hepatocarcinogenesis, apoptosis, and anti-oxidative pathways were differentially regulated by all compounds. Moreover, interaction networks showed that nuclear factor-κB (NF-κB) might play a central role in the regulation of the gene expression network. Further analysis revealed that these hepatoprotectants inhibited NF-κB activation in a dose-dependent manner. Conclusion: Our data suggested that glycyrrhizin, silymarin, and ursodeoxycholic acid protected livers from damage by regulating the genes involved in apoptosis and oxidative stress. Moreover, the regulation of genes by hepatoprotectants might be through the suppression of NF-κB activities. Overall design: We used an oligonucleotide microarray approach to study the gene expression profile in human hepatoma cells treated with 25 μM of hepatoprotective agents.