Protective effects of harpagoside on mitochondrial functions in rotenone‑induced cell models of Parkinson's disease

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Currently, no radical treatment is available for this disease. Harpagoside is a proposed neuroprotective iridoid active ingredient that can be derived from Scrophulariae buergeriana, Scrophularia striata and Harpagophytum procumbens. The present study aimed to investigate the effects of harpagoside on mitochondrial functions in rotenone-induced cell models of Parkinson's disease (PD). Neuro-2A (N2A) cells were treated with rotenone to establish in vitro cell models of PD. Cell viability and survival were measured using a Cell Counting Kit-8 assay. Biochemical assays with spectrophotometry were used to measure complex I activity, mitochondrial swelling and caspase 3 activity. The cell survival rate was first found to be significantly decreased by rotenone (20 nmol/l) treatment. However, intervention with harpagoside (10 µmol/l) was found to increase the cell survival rate of rotenone-induced N2A cell models differentiated with 1 mmol/l of dibutyryl-cAMP. At ≥0.1 µmol/l concentration, harpagoside significantly alleviated rotenone-induced mitochondrial swelling, whereas at 1 µmol/l it significantly counteracted the inhibitory effects of rotenone on complex I activity. At 10 µmol/l harpagoside significantly inhibited rotenone-induced caspase 3 activation. These results suggest that harpagoside has the potential to protect mitochondrial functions against rotenone-induced injury in N2A cell models of PD.