Bilobalide inhibits 6-OHDA-induced activation of NF-kappaB and loss of dopaminergic neurons in rat substantia nigra.
OBJECTIVE
To investigate the effects of bilobalide on the activation of NF-kappaB, and apoptosis of dopaminergic neurons induced by 6-hydroxydopamine (6-OHDA).


METHODS
A rat model of Parkinson's disease was produced with a unilateral infusion of 6-OHDA (8 mug) into the substantia nigra par compact. Bilobalide was administered 5, 10, and 20 mg/kg (ip) once a day for 7 d, starting 6 d prior to the 6- OHDA infusion. The rats were subjected to locomotor activity and rotational behavior testing 2 or 3 weeks after the 6-OHDA infusion. The expressions of tyrosine hydroxylase (TH) and NF-kappaB p65 were examined by immunofluorescence. The loss of dopaminergic neurons was detected by Nissl's staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to identify apoptosis.


RESULTS
The behavioral changes due to 6-OHDA were significantly restored by bilobalide pretreatment. Bilobalide inhibited the 6-OHDA-induced loss of TH-positive neurons, decreased the activation of NF-kappaB, and protected dopaminergic neurons from apoptosis remarkably.


CONCLUSIONS
NF-kappaB activation contributes to the 6-OHDA-induced loss of dopaminergic neurons, and the inhibition of the NF-kappaB pathway is likely to be involved in the neuroprotective effect of bilobalide.
Li
Ling-Yun
LY
Department of Pharmacology, Soochow University School of Medicine, Laboratory of Aging and Nervous Diseases, Soochow University School of Medicine, Suzhou 215123, China.
Zhao
Xi-Lin
XL
Fei
Xi-Feng
XF
Gu
Zhen-Lun
ZL
Qin
Zheng-Hong
ZH
Liang
Zhong-Qin
ZQ
D000818:Animals; D003517:Cyclopentanes / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology*; D046934:Ginkgolides / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology; D013565:Sympatholytics / Q000494:pharmacology
D003517:Cyclopentanes; D005663:Furans; D046934:Ginkgolides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D013565:Sympatholytics; D016627:Oxidopamine; C073710:bilobalide