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Effects of silymarin on hepatitis C virus and haem oxygenase-1 gene expression in human hepatoma cells

Authors

  • Vania Bonifaz,

    1. Departments of Microbial, Molecular, and Structural Biology, University of Connecticut Health Center, Farmington, CT, USA
    2. Department of The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA
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    • *Present Address: Vania Bonifaz P., Universidad de las Américas-Puebla, Ex Hacienda de Sta. Catarina Mártir, Cholula, Puebla, C.P. 72820, Mexico.

  • Ying Shan,

    1. Departments of Microbial, Molecular, and Structural Biology, University of Connecticut Health Center, Farmington, CT, USA
    2. Department of The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA
    3. Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA
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    • Present Address: Ying Shan, MD, Division of Preventative and Behavioral Medicine, University of Massachusetts School of Medicine, 55 Lake Avenue North, Worcester, MA 06111.

  • Richard W. Lambrecht,

    1. Department of The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA
    2. Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA
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    • Present Address: Richard Lambrecht, PhD, University of Connecticut Health Center, Department of Medicine, 263 Farmington Ave, Farmington, CT 06030.

  • Susan E. Donohue,

    1. Departments of Microbial, Molecular, and Structural Biology, University of Connecticut Health Center, Farmington, CT, USA
    2. Department of The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA
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  • Darcy Moschenross,

    1. Departments of Microbial, Molecular, and Structural Biology, University of Connecticut Health Center, Farmington, CT, USA
    2. Department of The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA
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    • §Present Address: Darcy Moschenross, University of Connecticut Health Center, L2012, 263 Farmington Avenue, Farmington, CT 06030-3205.

  • Herbert L. Bonkovsky

    1. Departments of Microbial, Molecular, and Structural Biology, University of Connecticut Health Center, Farmington, CT, USA
    2. Department of The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA
    3. Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA
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Correspondence
Herbert L. Bonkovsky, MD, Vice President for Research, Cannon Research Center, Carolinas Medical Center, Professor, University of Connecticut, Adjunct Professor, University of North Carolina, PO Box 32861, Charlotte, NC 28232-2861.
Tel: +704 355 3959
Fax: +704 3557648
e-mail: Herbert.bonkovsky@carolinashealthcare.org

Abstract

Background/Aims: 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.

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