Chrysotoxine, a novel bibenzyl compound selectively antagonizes MPP⁺, but not rotenone, neurotoxicity in dopaminergic SH-SY5Y cells

Neurosci Lett. 2012 Jul 11;521(1):76-81. doi: 10.1016/j.neulet.2012.05.063. Epub 2012 Jun 1.

Abstract

Chrysotoxine is a naturally occurring bibenzyl compound found in medicinal Dendrobium species. We previously reported that chrysotoxine structure-specifically suppressed 6-hydroxydopamine (6-OHDA)-induced dopaminergic cell death. Whether chrysotoxine and other structurally similar bibenzyl compounds could also inhibit the neurotoxicity of 1-methyl-4-phenyl pyridinium (MPP(+)) and rotenone has not been investigated. We showed herein that chrysotoxine inhibited MPP(+), but not rotenone, induced dopaminergic cell death in SH-SY5Y cells. The overproduction of reactive oxygen species (ROS), mitochondrial dysfunction as indexed by the decrease in membrane potential, increase in calcium concentration and NF-κB activation triggered by MPP(+) were blocked by chrysotoxine pretreatment. The imbalance between the pro-apoptotic signals (Bax, caspase-3, ERK and p38 MAPK) and the pro-survival signals (Akt/PI3K/GSK-3β) induced by MPP(+) was partially or totally rectified by chrysotoxine. The results indicated that ROS inhibition, mitochondria protection, NF-κB modulation and regulation of multiple signals determining cell survival and cell death were involved in the protective effects of chrysotoxine against MPP(+) toxicity in SH-SY5Y cells. Given the different toxic profiles of 6-OHDA and MPP(+) as compared to rotenone, our results also indicated that DAT inhibition may partially account for the neuroprotective effects of chrysotoxine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / antagonists & inhibitors*
  • 1-Methyl-4-phenylpyridinium / toxicity
  • Active Transport, Cell Nucleus
  • Antiparkinson Agents / pharmacology*
  • Bibenzyls / pharmacology*
  • Calcium / metabolism
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Dopamine / metabolism*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Reactive Oxygen Species / metabolism
  • Rotenone / antagonists & inhibitors*
  • Rotenone / toxicity
  • Transcription Factor RelA / metabolism

Substances

  • Antiparkinson Agents
  • Bibenzyls
  • Reactive Oxygen Species
  • Transcription Factor RelA
  • chrysotoxine
  • Rotenone
  • 1-Methyl-4-phenylpyridinium
  • Calcium
  • Dopamine