title: Effects of silymarin on hepatitis C virus and haem oxygenase-1 gene expression in human hepatoma cells.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) infection is a global medical problem. The current standard treatment of chronic hepatitis C (CHC), pegylated interferon plus ribavirin, is prolonged, expensive, has serious side effects and, at best, is only 50% effective. Silymarin (SI) is a natural antioxidant often used by patients with CHC, although its efficacy for decreasing HCV levels or ameliorating CHC remains uncertain. HCV infection is associated with increased hepatic oxidative stress, and one of the antioxidant enzymes that protect cells against this stress is haem oxygenase-1 (HO-1).
  
  
  METHODS
  We investigated effects of SI on HCV and HO-1 gene expression in Huh-7 cells, CNS3 and 9-13 cells (the latter two stably expressing HCV-proteins).
  
  
  RESULTS
  Silymarin significantly downregulated HCV core mRNA (by 20%-36%) and protein (by 30%-60%) in CNS3 cells. In contrast, SI did not decrease HCV NS5A mRNA or protein expression in 9-13 cells. HO-1 mRNA was upregulated (60%-400%) by SI in Huh-7, CNS3 and 9-13 cells, whereas BTB and CNC homology 1 and nuclear factor erythroid related factor 2 mRNA levels were not affected. The effect of SI to downregulate HCV core was not related to changes in the Janus-activated tyrosine kinases-signal transducer and activators of transcription signalling pathway.
  
  
  CONCLUSIONS
  Silymarin may be of benefit in CHC, although prospective, randomized, controlled trials are needed to be certain.
authors.affiliation: Department of Microbial Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Vania
authors.initials: V
authors.lastname: Bonifaz
authors.forename: Ying
authors.initials: Y
authors.lastname: Shan
authors.forename: Richard W
authors.initials: RW
authors.lastname: Lambrecht
authors.forename: Susan E
authors.initials: SE
authors.lastname: Donohue
authors.forename: Darcy
authors.initials: D
authors.lastname: Moschenross
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000821:virology; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012838:Silymarin / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D017931:DNA Primers; D012838:Silymarin; D013778:Tetrazolium Salts; D013844:Thiazoles; D006419:Heme Oxygenase (Decyclizing); C022616:thiazolyl blue