Curcumin inhibits HMGB1 releasing and attenuates concanavalin A-induced hepatitis in mice

Eur J Pharmacol. 2012 Dec 15;697(1-3):152-7. doi: 10.1016/j.ejphar.2012.09.050. Epub 2012 Oct 11.

Abstract

Curcumin, a polyphenol extracted from the plant curcuma longa, exhibits a number of pharmacological properties and has been used for the treatment of inflammatory diseases. However, the potential protective effects of curcumin in inflammatory liver diseases have not been clearly elucidated. Thus, the current study aimed to investigate the beneficial effects of curcumin on hepatic injury induced by concanavalin A (Con A), and its possible molecular mechanisms in mice. Acute live injury model was established successfully by intravenous administration of Con A (15mg/kg) in male C57BL/6 mice. Curcumin was administered to mice 2h prior to Con A injection. It was found that curcumin pretreatment significantly protected animals from T cell-mediated hepatitis as evidenced by decreased elevation of serum ALT, associated with reduced hepatic necrosis, apoptosis and mortality. In addition, curcumin pretreatment markedly reduced hepatic oxidative stress and pro inflammatory cytokines, including TNF-α and IFN-γ. Furthermore, curcumin pretreatment dramatically suppressed the releasing of high-mobility group box-1 (HMGB1) in liver tissues. These results suggest that curcumin pretreatment protects the mice from Con A-induced liver injury via inhibiting hepatocyte oxidative stress, inflammation and releasing of HMGB1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Biomarkers / blood
  • Concanavalin A*
  • Curcumin / pharmacology*
  • Cytoprotection
  • Disease Models, Animal
  • Down-Regulation
  • HMGB1 Protein / metabolism*
  • Hepatitis, Autoimmune / etiology
  • Hepatitis, Autoimmune / metabolism
  • Hepatitis, Autoimmune / pathology
  • Hepatitis, Autoimmune / prevention & control*
  • Interferon-gamma / blood
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Necrosis
  • Oxidative Stress / drug effects
  • Time Factors
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Biomarkers
  • HMGB1 Protein
  • Tumor Necrosis Factor-alpha
  • Concanavalin A
  • Malondialdehyde
  • Interferon-gamma
  • Alanine Transaminase
  • Curcumin