Chrysotoxine, a novel bibenzyl compound, inhibits 6-hydroxydopamine induced apoptosis in SH-SY5Y cells via mitochondria protection and NF-κB modulation

Ju Xian Song, Pang Chui Shaw, Cho Wing Sze, Yao Tong, Xin Sheng Yao, Tzi Bun Ng, Yan Bo Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Some naturally occurring bibenzyl compounds have been reported as free radical scavengers. The present study tested our hypothesis that bibenzyl compounds may be neuroprotective against apoptosis induced by the neurotoxins. Five structurally similar bibenzyl derivatives were tested for their protective effect against 6-hydroxydopamine (6-OHDA) induced toxicity in the human neuroblastoma cell line SH-SY5Y. The results showed that one bibenzyl compound, namely chrysotoxine, significantly attenuated 6-OHDA-induced cell death. The subsequent mechanism study demonstrated that chrysotoxine significantly attenuated 6-OHDA-induced apoptosis characterized by DNA fragmentation and nuclear condensation in a dose-dependent manner. 6-OHDA-induced intracellular generation of reactive oxygen species (ROS), activation of p38 MAPK and ERK1/2, and mitochondrial dysfunctions, including the decrease of membrane potential, increase of intracellular free Ca2+, release of cytochrome c, imbalance of Bax/Bcl-2 ratio and activation of caspase-3 were strikingly attenuated by chrysotoxine pretreatment. Meanwhile, chrysotoxine counteracted NF-κB activation by blocking its translocation to the nucleus, thereby preventing up-regulation of inducible nitric oxide synthase (iNOS) and intracellular NO release. The data provide the first evidence that chrysotoxine protects SH-SY5Y cells against 6-OHDA toxicity possibly through mitochondria protection and NF-κB modulation. Chrysotoxine is thus a candidate for further evaluation of its protection against neurodegeneration in Parkinson's disease.
Original languageEnglish
Pages (from-to)676-689
Number of pages14
JournalNeurochemistry International
Volume57
Issue number6
DOIs
Publication statusPublished - Nov 2010
Externally publishedYes

Scopus Subject Areas

  • Neuroscience(all)

User-Defined Keywords

  • Parkinson's disease
  • Chrysotoxine
  • Apoptosis
  • Reactive oxygen species
  • Mitochondrial dysfunctions
  • NF-κB

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