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

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. We used an oligonucleotide microarray approach to study the gene expression profile in human hepatoma cells treated with 25 μM of hepatoprotective agents.

背景：甘草酸、水飞蓟宾与熊去氧胆酸是临床广泛应用的保肝剂（hepatoprotectant），用于治疗丙型肝炎病毒感染、原发性胆汁性肝硬化、肝细胞癌等肝脏疾病。
假说/研究目的：然而，目前鲜有研究探讨此类化合物对基因表达的调控作用。
方法：本研究采用寡核苷酸微阵列（oligonucleotide microarray）技术，分析25 μM保肝剂处理后人肝癌细胞的基因表达谱（gene expression profile）。
结果：在全部30968个检测基因中，共有252个基因可被三类化合物共同调控。此类化合物可影响参与不同生物学通路的基因表达，包括神经传递、糖脂代谢等通路。参与肝细胞癌变、细胞凋亡及抗氧化通路的基因，也均被三类化合物差异化调控。进一步的相互作用网络分析显示，核因子-κB（NF-κB）可能在该基因表达调控网络中发挥核心作用。后续实验发现，此类保肝剂可通过剂量依赖方式抑制NF-κB的活化。
结论：本研究数据表明，甘草酸、水飞蓟宾及熊去氧胆酸可通过调控参与细胞凋亡与氧化应激的基因，发挥肝脏保护作用。此外，保肝剂对基因表达的调控可能通过抑制NF-κB的活性实现。本研究采用寡核苷酸微阵列技术，分析25 μM保肝剂处理后人肝癌细胞的基因表达谱。