Multiple Effects of Silymarin on the Hepatitis C Virus Lifecycle

Research output: Contribution to journalArticlepeer-review

Authors

  • J Wagoner
  • A Negash
  • OJ Kane
  • LE Martinez
  • Y Nahmias
  • N Bourne
  • DM Owen
  • C Brimacombe
  • EI Pecheur
  • TN Graf
  • NH Oberlies
  • V Lohmann
  • F Cao
  • JE Tavis
  • SJ Polyak

Colleges, School and Institutes

Abstract

Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit hepatitis C virus (HCV) infection, both in vitro and in vivo. In the current study, we further characterized silymarin's antiviral actions. Silymarin had antiviral effects against hepatitis C virus cell culture (HCVcc) infection that included inhibition of virus entry, RNA and protein expression, and infectious virus production. Silymarin did not block HCVcc binding to cells but inhibited the entry of several viral pseudoparticles (pp), and fusion of HCVpp with liposomes. Silymarin but not silibinin inhibited genotype 2a NS5B RNA-dependent RNA polymerase (RdRp) activity at concentrations 5 to 10 times higher than required for anti-HCVcc effects. Furthermore, silymarin had inefficient activity on the genotype 1b BK and four 1b RDRPs derived from HCV-infected patients. Moreover, silymarin did not inhibit HCV replication in five independent genotype 1a, 1b, and 2a replicon cell lines that did not produce infectious virus. Silymarin inhibited microsomal triglyceride transfer protein activity, apolipoprotein B secretion, and infectious virion production into culture supernatants. Silymarin also blocked cell-to-cell spread of virus. CONCLUSION: Although inhibition of in vitro NS5B polymerase activity is demonstrable, the mechanisms of silymarin's antiviral action appear to include blocking of virus entry and transmission, possibly by targeting the host cell.

Details

Original languageEnglish
Pages (from-to)1912-1921
Number of pages10
JournalHepatology
Volume51
Issue number6
Publication statusPublished - 1 Jun 2010