Neuroprotective and neurotrophic effects of ginkgetin and bilobalide on MPTP-induced mice with Parkinson' disease

Objectives: The neuroprotective and neurotrophic effects of natural products ginkgetin and bilobalide were investigated to explore their underlying mechanisms in Parkinson's disease (PD). Methods: Mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (25 mg/kg) and probenecid (250 mg/kg) for five consecutive days to induce PD. Ginkgetin (5, 10, 20 mg/kg), bilobalide (10, 20 mg/kg) and bromocriptine (10 mg/kg) were administered orally for 26 days including five days of pretreatment in Parkinson mice respectively. Subsequently, behavior analysis and oxidative stress were detected. Tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF) in the substantia nigra (SN) were tested by immunostaining method. ELISA was used to detect tumor necrosis factor-α (TNF-α). Results: In MPTP-induced PD mice, movements and muscle functions improved by ginkgetin and bilobalide. TH positive cells were reduced to 7% (P < 0.001) and then recovered to 69% and 63% after treatment, later with no degenerations (P < 0.001). The GFAP levels decreased, while the BDNF levels increased significantly after treatment of ginkgetin and bilobalide. Conclusions: Ginkgetin and bilobalide showed effective dopaminergic neurons protection by reducing oxidative damage, activating microglial, and enhancing the potential of neurotrophic, which demonstrated that the two natural products were prospective candidates for the treatment of PD.