Acta Pharmacologica Sinica 2008 May; 29 (5): 539-547; doi: 10.1111/j.1745-7254.2008.00787.x

Aim: To investigate the effects of bilobalide on the activation of NF-κB, 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 µg) 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-κB 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-κB, and protected dopaminergic neurons from apoptosis remarkably.

Conclusion: NF-κB activation contributes to the 6-OHDA-induced loss of dopaminergic neurons, and the inhibition of the NF-κB pathway is likely to be involved in the neuroprotective effect of bilobalide.

Keywords: bilobalide; 6-hydroxydopamine; Parkinson's disease; NF-κB; apoptosis