Ming Hu, Fangming Li, Weidong Wang

Parkinson's disease (PD) is a progressive neurodegenerative disease which is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). In this study, the neuroprotective effect of vitexin (Vit), a flavonoid compound isolated from Crataegus pinnatifida Bunge was examined in PD models both in vitro and in vivo. On SH-SY5Y cells, methyl-4-phenylpyridine (MPP+) treatment suppressed cell viability, induced apoptosis, and increased Bax/Bcl-2 ratio and caspase-3 activity. However, Vit improved these parameters induced by MPP+ treatment significantly. Further study disclosed that Vit enhanced the phosphorylation of PI3K and Akt which was downregulated by MPP+ in SH-SY5Y cells, the effect of which could be blocked by PI3K inhibitor LY294002 and activated by PI3K activator IGF-1. Moreover, results from the pole test and traction test suggested that Vit pretreatment prevented bradykinesia and alleviated the initial lesions caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in MPTP-treated mouse PD model. Vit also enhanced the activation of PI3K and Akt and suppressed the ratio of Bax/Bcl-2 and caspase-3 activity in MPTP-treated mice. Taken together, this study demonstrated that Vit protected dopaminergic neurons against MPP+/MPTP-induced neurotoxicity through the activation of PI3K/Akt signaling pathway. Our findings may facilitate the clinical application of Vit in the therapy of PD.