Ameliorative effect of betulinic acid on oxidative damage and apoptosis in the splenocytes of dexamethasone treated mice

Int Immunopharmacol. 2015 Jul;27(1):85-94. doi: 10.1016/j.intimp.2015.04.050. Epub 2015 May 7.

Abstract

Betulinic acid (BA) is a bioactive pentacyclic triterpene that exhibits a variety of biological activities including antioxidative and immunomodulative properties. The objective of this study was to investigate the potential splenocytes protective effect and underlying mechanism of BA using dexamethasone (Dex)-induced mice as a model system. Pretreatment with BA (0.25, 0.5, and 1.0 mg/kg) dose-dependently ameliorated Dex-induced oxidative damage and apoptosis after 14 days of feeding. In addition to reactive oxygen species scavenging activity in Dex-induced splenocytes, BA administration up-regulated antioxidant enzymes, decreased lipid peroxidation, restored mitochondrial function, decreased the expression of pro-apoptotic protein Bax, prevented the decline of anti-apoptotic protein Bcl-2, inhibited caspase-9 and caspase-3 activation, and improved cell survival. These findings reveal that BA was able to mitigate Dex-induced oxidative stress and might play an important role in repairs of oxidative damage in immunological system.

Keywords: Apoptosis; Betulinic acid; Dexamethasone; Oxidative stress; Splenocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Apoptosis / drug effects
  • Betulinic Acid
  • Caspase 3 / metabolism
  • Cell Survival / drug effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Lipid Peroxidation / drug effects
  • Mice
  • Mice, Inbred Strains
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects*
  • Pentacyclic Triterpenes
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Spleen / immunology*
  • Spleen / pathology
  • Triterpenes / administration & dosage*
  • Triterpenes / adverse effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Pentacyclic Triterpenes
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Triterpenes
  • Dexamethasone
  • Caspase 3
  • Betulinic Acid