Aqueous leaf extract of Sutherlandia frutescens attenuates ROS-induced apoptosis and loss of mitochondrial membrane potential in MPP+-treated SH-SY5Y cells

Purpose: To investigate the neuroprotective activity of the aqueous extract of Sutherlandia frutescens (SF) against 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in SH-SY5Y neuroblastoma cells. Methods: SH-SY5Y neuroblastoma cells were divided into different treatment groups: untreated cells, cells treated with MPP+ alone (2 mM), cells pretreated with SF (20 μg) prior to MPP+ (2 mM) treatment and cells treated with SF (20 μg) alone. Twenty-four hours after treatment with MPP+, cell viability was assessed by MTT assay, and changes in cell morphology, intracellular reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) as well as caspases 3/7 and 9 activities were determined. Results: Treatment of SH-SY5Y cells with MPP+ alone significantly altered cellular morphology, increased ROS production (p = 0.005), induced a significant loss of MMP (p = 0.0011) and caused significant apoptotic cell death, via the activation of caspases 3/7 and 9 (p ≤ 0.0359). These effects were however significantly (p ≤ 0.0359) attenuated in cells pre-treated with the aqueous leaf extract of SF, indicating the possible neuroprotective activity of the SF extract. Conclusion: The results of this study suggest that the aqueous leaf extract of SF may be neuroprotective against MPP+-induced toxicity via apoptotic cell death and inhibition of ROS production. Further mechanistic studies are required to validate the results of the present study using additional PD models, different extract preparations and active compounds derived from SF. Keywords: Parkinson’s disease, MPP+, Sutherlandia frutescens, Reactive oxygen species, Apoptosis, Neurodegeneration