Anti-hepatitis C virus activity of 3-hydroxy caruilignan C from Swietenia macrophylla stems

J Viral Hepat. 2012 May;19(5):364-70. doi: 10.1111/j.1365-2893.2011.01558.x. Epub 2011 Nov 24.

Abstract

Chronic hepatitis C virus (HCV) infection ultimately leads to chronic hepatitis, hepatic cirrhosis and hepatocellular carcinoma (HCC). As the standard treatment is not completely efficacious, a safer and more effective agent against HCV infection needs to be developed. In this report, we demonstrated that 3-hydroxy caruilignan C (3-HCL-C) isolated from Swietenia macrophylla stems exhibited high anti-HCV activity at both protein and RNA levels at nontoxic concentrations, with an EC(50) value of 10.5 ± 1.2 μm. Combinations of 3-HCL-C and interferon-α (IFN-α), an HCV NS5B polymerase inhibitor (2'-C-methylcytidine; NM-107) or an HCV NS3/4A protease inhibitor (Telaprevir; VX-950) increased the suppression of HCV RNA replication. The results suggested that 3-HCL-C may be a potential anti-viral agent. We then demonstrated that 3-HCL-C interfered with HCV replication by inducing IFN-stimulated response element transcription and IFN-dependent anti-viral gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology*
  • Hepacivirus / drug effects*
  • Humans
  • Interferon-alpha / pharmacology
  • Lignans / chemistry
  • Lignans / isolation & purification
  • Lignans / pharmacology*
  • Meliaceae / chemistry*
  • Microbial Sensitivity Tests
  • Oligopeptides / pharmacology
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Stems / chemistry
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Lignans
  • Oligopeptides
  • Plant Extracts
  • telaprevir