Chrysotoxine, a novel bibenzyl compound, inhibits 6-hydroxydopamine induced apoptosis in SH-SY5Y cells via mitochondria protection and NF-κB modulation.
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.
Song
Ju-Xian
JX
The School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Shaw
Pang-Chui
PC
Sze
Cho-Wing
CW
Tong
Yao
Y
Yao
Xin-Sheng
XS
Ng
Tzi-Bun
TB
Zhang
Yan-Bo
YB
D017209:Apoptosis / Q000187:drug effects*; D001632:Bibenzyls / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D016627:Oxidopamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
D001632:Bibenzyls; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C555497:chrysotoxine; D016627:Oxidopamine