Sodium tanshinone IIA sulfonate protects mice from ConA-induced hepatitis via inhibiting NF-kappaB and IFN-gamma/STAT1 pathways

J Clin Immunol. 2008 Sep;28(5):512-9. doi: 10.1007/s10875-008-9206-3. Epub 2008 May 24.

Abstract

Introduction: Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, the main pharmacologically active component of Salvia miltiorrhiza. The aim of this study was to investigate the effect of STS on concanavalin A (ConA)-induced hepatitis (CIH) in mice, an experimental model of immune-mediated liver injury.

Results: C57BL/6 mice pretreated with STS released much less alanine transaminase into plasma in response to ConA challenge and had reduced inflammatory infiltration and hepatocyte apoptosis in the liver compared with control mice pretreated with vehicle solutions. Thus, STS protected mice from CIH. In STS-pretreated mice induced with CIH, we found abrogated tumor necrosis factor-alpha and interferon (IFN)-gamma production. Moreover, mRNA expressions of IFN-inducible protein-10 and macrophage inflammatory protein-1alpha in these mice were decreased. The mechanism of anti-inflammatory effects of STS may be attributed to its modulation of crucial inflammatory signaling pathways, including NF-kappaB and IFN-gamma/STAT1.

Conclusion: In conclusion, STS was capable of protecting mice from immune-mediated liver injury in vivo, and the protection was associated with its suppressive effect on the production of important inflammatory mediators through modulating NF-kappaB and IFN-gamma/STAT1 signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Concanavalin A / toxicity
  • Hepatitis, Animal / chemically induced
  • Hepatitis, Animal / drug therapy*
  • Hepatitis, Animal / immunology
  • Hepatitis, Animal / metabolism
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / immunology
  • Injections, Intraperitoneal
  • Interferon-gamma / blood
  • Interferon-gamma / immunology*
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / immunology
  • Phenanthrenes / administration & dosage*
  • Phenanthrenes / chemistry
  • Phenanthrenes / immunology
  • Phytotherapy
  • STAT1 Transcription Factor / immunology
  • STAT1 Transcription Factor / metabolism*
  • Salvia miltiorrhiza / immunology
  • Signal Transduction / drug effects*
  • Signal Transduction / immunology
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Immunosuppressive Agents
  • NF-kappa B
  • Phenanthrenes
  • STAT1 Transcription Factor
  • Tumor Necrosis Factor-alpha
  • Concanavalin A
  • tanshinone II A sodium sulfonate
  • Interferon-gamma