Protective effects of three herbal extracts on mitochondrial dysfunction in VPS13C-knockdown SH-SY5Y cells: implications for Parkinson's disease.

Parkinson's disease (PD) results primarily from the loss of midbrain dopaminergic neurons. Mitochondrial dysfunction may contribute to PD pathogenesis and depletion of vacuolar protein sorting 13 homolog C (VPS13C) leads to mitochondrial dysfunction. Traditional Chinese medicine (TCM) extracts Uncaria rhynchophylla, Gardenia jasminoides, and Scutellaria baicalensis were reported to have anti-PD effects. This study aimed to examine these three extracts for enhancing VPS13C expression and mechanisms of neuroprotection. Using FCCP-mediated oxidative phosphorylation uncoupling or RNA interference-directed VPS13C knockdown, reduced cell viability and mitochondrial membrane potential (MMP) accompanied with increased mitochondrial superoxide in human neuroblastoma SH-SY5Y cells were established. Treatment of cells with these extracts increased cell viability, MMP, and reduced the mitochondrial superoxide. In differentiated SH-SY5Y cells with VPS13C knockdown, these extracts reduced lactate dehydrogenase release, caspase-3 activity, reactive oxygen species production, and promoted neurite outgrowth. The extracts increased VPS13C, superoxide dismutase (SOD) 1 and 2, nuclear respiratory factor 2 (NRF2), PPARG coactivator 1 alpha (PGC-1α), and B-cell lymphoma 2 (BCL2) expression in these cells, accompanied by increases in MMP, mitochondrial mass, and reduction in mitochondrial superoxide. In conclusion, treatments with these three TCM compounds reduced mitochondrial dysfunction and oxidative stress in VPS13C-knockdown cells, making them potential drug candidates for PD.