Neuroprotective effects of paederoside against mitochondrial dysfunction in rotenone-induced cell models of Parkinson’s disease

IntroductionParkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is one of the leading causes of neurological disability. Although there are currently no cures or treatments for this disease, many patients with PD may therapeutically benefit from preventing or mitigating mitochondrial dysfunction. This study aimed to investigate the protective effects of paederoside against rotenone-induced neuronal damage in Neuro-2A (N2A) cell models of PD.MethodsFirst, the cytotoxic effects of rotenone on N2A cells were assessed using the cell counting kit-8 assay to establish a cell model of PD. Second, the effects of paederoside on mitochondrial complex I activity, mitochondrial swelling, and caspase-3 activity in the rotenone-induced cellular model were investigated. Finally, the impact of paederoside on tyrosine hydroxylase-positive cells in a rotenone-induced co-culture of N2A cells and BV-2 cells (N2A/BV-2) was studied.ResultsN2A cells were significantly damaged by rotenone in a time- and concentration-dependent manner; a 48 h rotenone treatment at 20 nM was used to create a cell model of PD. Pretreatment with 1 μM paederoside notably increased mitochondrial complex I activity in N2A cells with rotenone-induced impairment, leading to 42.85% increase. Additionally, pretreatment with 0.1, 1, and 10 μM paederoside considerably alleviated rotenone-induced mitochondrial swelling as indicated by the optical density (OD) (10 min)/OD(0 min) ratio, which increased by 1.21-, 1.33-, and 1.37-fold, respectively. Notably, pretreatment with 10 μM paederoside significantly inhibited caspase-3 activation triggered by rotenone in this cellular setting, resulting in a 39.93% decrease in enzyme activity. Moreover, pretreatment with 10 μM of paederoside markedly enhanced the number of TH-positive cells in a co-culture system consisting of N2A/BV-2 cells induced by rotenone, with increases of 82.79%.ConclusionPretreatment with paederoside may protect against mitochondrial dysfunction in cell models of PD induced by rotenone.