title: Glycyrrhizin, silymarin, and ursodeoxycholic acid regulate a common hepatoprotective pathway in HepG2 cells.
abstract: 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.
  
  
  OBJECTIVE
  The gene expression profiles of HepG2 cells responsive to glycyrrhizin, silymarin, and ursodeoxycholic acid were analyzed in this study.
  
  
  METHODS
  HepG2 cells were treated with 25 µM hepatoprotectants for 24 h. Gene expression profiles of hepatoprotectants-treated cells were analyzed by oligonucleotide microarray in triplicates. Nuclear factor-κB (NF-κB) activities were assessed by luciferase assay.
  
  
  RESULTS
  Among a total of 30,968 genes, 252 genes were commonly regulated by glycyrrhizin, silymarin, and ursodeoxycholic acid. These compounds affected the expression of genes relevant various 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 NF-κB might play a central role in the regulation of gene expression. Further analysis revealed that these hepatoprotectants inhibited NF-κB activities in a dose-dependent manner.
  
  
  CONCLUSIONS
  Our data suggested that glycyrrhizin, silymarin, and ursodeoxycholic acid regulated the expression of genes relevant to apoptosis and oxidative stress in HepG2 cells. Moreover, the regulation by these hepatoprotectants might be relevant to the suppression of NF-κB activities.
authors.affiliation: Department of Microbiology, China Medical University, Taichung 40402, Taiwan.
authors.forename: Chien-Yun
authors.initials: CY
authors.lastname: Hsiang
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Shung-Te
authors.initials: ST
authors.lastname: Kao
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Lo
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Shun-Ting
authors.initials: ST
authors.lastname: Chou
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan. Electronic address: cyhsiang@mail.cmu.edu.tw.
authors.forename: Tin-Yun
authors.initials: TY
authors.lastname: Ho
mesh_terms: D017209:Apoptosis; D005786:Gene Expression Regulation; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D020011:Protective Agents / Q000494:pharmacology*; D012838:Silymarin / Q000494:pharmacology*; D059467:Transcriptome; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D020011:Protective Agents; D012838:Silymarin; D019695:Glycyrrhizic Acid; D014580:Ursodeoxycholic Acid
keywords: Glycyrrhizin; Hepatoprotectants; Microarray; Silymarin; Ursodeoxycholic acid