3-O-demethylswertipunicoside inhibits MPP⁺-induced oxidative stress and apoptosis in PC12 cells

Brain Res. 2013 May 1:1508:53-62. doi: 10.1016/j.brainres.2013.02.049. Epub 2013 Mar 7.

Abstract

The 3-O-demethylswertipunicoside (3-ODS) is extracted from Swertia punicea. Recent study from our laboratory has demonstrated that the 3-ODS protects against oxidative toxicity and apoptosis in PC12 cells (Zhang, S.P., Du, X.G., Pu, X.P., 2010. Biol. Pharm. Bull. 33, 1529-1533). The aim of our study is to further investigate the neuroprotective mechanisms of 3-ODS in 1-methyl-4-phenylpyridinium (MPP(+))-induced neurotoxicity in PC12 cells. The results indicated that pre-treatment with 3-ODS significantly increased the cell viability compared with MPP(+) treatment. It also alleviated the oxidative stress by increasing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) level and reactive oxygen specise (ROS) production. Moreover, 3-ODS also attenuated MPP(+)-induced apoptosis by inhibiting Bax and Bcl-2 expressions, activating caspase-9, caspase-3, poly (ADP-ribose) polymerase-1 (PARP-1) cleavage, apoptosis-inducing factor (AIF) translocation and α-synuclein expression. These results suggest that 3-ODS might has applications as a complementary medicine for the treatment of Parkinson's disease (PD) or other neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / antagonists & inhibitors*
  • 1-Methyl-4-phenylpyridinium / toxicity*
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Inducing Factor / metabolism
  • Blotting, Western
  • Dopamine Agents / toxicity*
  • Glucosides / pharmacology*
  • Malondialdehyde / metabolism
  • Mitochondria / drug effects
  • Neuroprotective Agents*
  • Oxidative Stress / drug effects*
  • PC12 Cells
  • Protein Transport
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Reactive Oxygen Species
  • Signal Transduction / drug effects
  • Superoxide Dismutase / metabolism
  • Xanthones / pharmacology*
  • alpha-Synuclein / antagonists & inhibitors
  • alpha-Synuclein / biosynthesis
  • bcl-2-Associated X Protein / metabolism

Substances

  • 3-O-demethylswertipunicoside
  • Apoptosis Inducing Factor
  • Dopamine Agents
  • Glucosides
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Xanthones
  • alpha-Synuclein
  • bcl-2-Associated X Protein
  • Malondialdehyde
  • Superoxide Dismutase
  • 1-Methyl-4-phenylpyridinium