Protective effects of a compound isolated from Alnus japonica on oxidative stress-induced death in transformed retinal ganglion cells

Food Chem Toxicol. 2013 Jun:56:425-35. doi: 10.1016/j.fct.2013.02.052. Epub 2013 Mar 14.

Abstract

Here, we investigated whether hirsutenone, a compound isolated from Alnus japonica, was able to attenuate oxidative stress-induced death in transformed retinal ganglion (RGC-5) cells. Hirsutenone effectively protected RGC-5 cells from oxidative insult induced by, l-buthionine-(S,R)-sulfoximine (BSO) plus glutamate in a concentration-dependent manner, as demonstrated by propidium iodide (PI)/Hoechst 33342 double staining, flow cytometry, and MTT assays. Moreover, hirsutenone inhibited the increase in apoptotic protein expression resulting from BSO plus glutamate. Hirsutenone also effectively inhibited sodium nitroprusside (SNP)-induced lipid peroxidation in rat brain homogenates. To investigate the effects of hirsutenone in vivo, we used N-methyl-d-aspartate (NMDA) as a negative insult on the retinas of rats. NMDA affects the thinning of the inner plexiform layer (IPL) and causes an increase in the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive ganglion cells in the ganglion cell layer (GCL). Hirsutenone treatment led to a reduction in NMDA-induced IPL and TUNEL staining of the GCL. In conclusion, hirsutenone isolated from A. japonica may act as neuroprotective agent for conditions such as glaucoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alnus / chemistry*
  • Animals
  • Apoptosis / drug effects
  • Buthionine Sulfoximine / adverse effects
  • Buthionine Sulfoximine / metabolism
  • Catechols / pharmacology
  • Cell Survival / drug effects
  • DNA Nucleotidylexotransferase / metabolism
  • Diarylheptanoids / pharmacology
  • Glaucoma / drug therapy
  • Glaucoma / prevention & control
  • Glutamic Acid / adverse effects
  • Glutamic Acid / metabolism
  • In Situ Nick-End Labeling
  • Lipid Peroxidation / drug effects
  • Male
  • N-Methylaspartate / adverse effects
  • N-Methylaspartate / antagonists & inhibitors
  • Neuroprotective Agents / pharmacology*
  • Nitroprusside / adverse effects
  • Nitroprusside / metabolism
  • Oxidative Stress / drug effects*
  • Plant Extracts / pharmacology*
  • Propidium / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Retina / drug effects
  • Retina / metabolism
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / metabolism
  • Thiobarbituric Acid Reactive Substances / chemistry

Substances

  • Catechols
  • Diarylheptanoids
  • Neuroprotective Agents
  • Plant Extracts
  • Thiobarbituric Acid Reactive Substances
  • hirsutenone
  • Nitroprusside
  • Propidium
  • Glutamic Acid
  • Buthionine Sulfoximine
  • N-Methylaspartate
  • DNA Nucleotidylexotransferase