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

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). 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). 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. Silymarin may be of benefit in CHC, although prospective, randomized, controlled trials are needed to be certain.