BackgroundParkinson's disease (PD) is a neurodegenerative disease featured by the pathological dysfunction of nigrostriatal dopaminergic neurons, which can cause an insufficient release of dopamine (DA), induce motor and nonmotor symptoms. Hyperoside (HYP) belongs to lignan components and has anti-inflammatory, antioxidant and neuroprotective effects. This study aimed to investigate the neuroprotective effects of HYP on dopaminergic neurons.Methods and resultsIn this study, MPTP and its active neurotoxic metabolite MPP+ were applied to establish the PD model, respectively, treated with HYP. We found that HYP (100μg/ml) mitigated the cytotoxicity effect of SH-SY5Y cells under the treatment of MPP+ and HYP (25mg/kg/d) alleviated the motor symptoms of PD mice induced by MPTP. HYP treatment reduced the content of NO, H2O2 and malondialdehyde (MDA) as well as mitochondrial damage of DA neurons both in vitro and in vivo. Meanwhile, HYP treatment converted neurotrophic factors' downregulation levels, including GDNF, BDNF and CNDF in vivo but not in nitro. Finally, we found there was an activation of AKT signaling after the administration of HYP in MPP+/MPTP model, and the inhibition of AKT signaling did not block the neuroprotection of HYP on DA neurons. ConclusionsThese results indicate that HYP protected the DA neurons from the MPP+ and MPTP-induced injuries in a way that did not rely on the AKT signal.
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