Protective effects of garcinol in mice with lipopolysaccharide/D-galactosamine-induced apoptotic liver injury

Int Immunopharmacol. 2014 Apr;19(2):373-80. doi: 10.1016/j.intimp.2014.02.012. Epub 2014 Feb 21.

Abstract

Garcinol is a polyisoprenylated benzophenone derivative of Garcinia indica. Recent researches have revealed the antioxidant, anticancer and anti-inflammatory properties of garcinol. In the present study, the pharmacological effects of garcinol in lipopolysaccharide (LPS)-induced hepatic injury in D-galactosamine (D-Gal)-sensitized mice were investigated. We found that treatment with garcinol significantly decreased serum ALT and AST levels in LPS/D-Gal-exposed mice. These were accomplished with improved histological alterations in liver sections and reduced malondialdehyde (MDA) content in liver homogenates. Garcinol significantly reduced the acetylation level of NF-κB, but it had no obvious effects on the elevation of TNF-α or IL-6 in plasma or liver tissue. Garcinol significantly attenuated LPS/D-Gal-induced hepatic apoptosis as evidenced by reduced number of TUNEL-positive cells in liver sections. Our experiments also showed that garcinol markedly suppressed the cleavage of caspase-3 and significantly decreased the activities of caspase-3, -8, and -9 in liver tissues. In addition, garcinol obviously reduced the induction of Bax but did not alter the level of Bcl-2. These results indicated that garcinol might provide protective benefits in LPS/D-Gal-induced liver injury through suppressing apoptosis.

Keywords: Apoptosis; Garcinol; Histone acetyltransferase; Lipopolysaccharide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Apoptosis / drug effects
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Galactosamine
  • Histone Acetyltransferases / antagonists & inhibitors
  • Interleukin-6 / metabolism
  • Lipopolysaccharides
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Terpenes / pharmacology
  • Terpenes / therapeutic use*
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, mouse
  • Interleukin-6
  • Lipopolysaccharides
  • Protective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Terpenes
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Galactosamine
  • Histone Acetyltransferases
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • garcinol