title: Bilobalide inhibits 6-OHDA-induced activation of NF-kappaB and loss of dopaminergic neurons in rat substantia nigra.
abstract: 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.
authors.affiliation: Department of Pharmacology, Soochow University School of Medicine, Laboratory of Aging and Nervous Diseases, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Li
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Zhao
authors.forename: Xi-Feng
authors.initials: XF
authors.lastname: Fei
authors.forename: Zhen-Lun
authors.initials: ZL
authors.lastname: Gu
authors.forename: Zheng-Hong
authors.initials: ZH
authors.lastname: Qin
authors.forename: Zhong-Qin
authors.initials: ZQ
authors.lastname: Liang
mesh_terms: 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
chemical_list: D003517:Cyclopentanes; D005663:Furans; D046934:Ginkgolides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D013565:Sympatholytics; D016627:Oxidopamine; C073710:bilobalide