Neuroprotective effects of polyphyllin VI against rotenone-induced toxicity in SH-SY5Y cells

Background: A substantial body of evidence is drawing connections between Parkinson's disease (PD) and the phenomena of oxidative stress and mitochondrial dysfunction. Polyphyllin VI (PPVI), an active compound found in Rhizoma Paridis-commonly known as Chonglou (CL) in China, has been identified for its various pharmacological properties, including anti-tumor and anti-inflammatory effects. Objective: In the present study, an in vitro model of PD was established by treating SH-SY5Y cells with rotenone (ROT), to evaluate the potential neuroprotective effects of polyphyllin VI and its underlying mechanism. Methods: SH-SY5Y cells were treated with ROT to establish an in vitro model of PD. The effects of polyphyllin VI on cell viability were assessed using the resazurin assay. Cell morphology was examined using a microscope. The YO-PRO-1/PI was used to detect apoptosis. Mito-Tracker Red CMXRos, Mito-Tracker Green, and JC-1 were used to detect the effects of polyphyllin VI on mitochondrial viability, morphology, and function. Oxidative stress-related marker detection kits were used to identify the effects of polyphyllin VI on oxidative stress. Western blot analysis was employed to investigate the signaling pathways associated with neuroprotection. Results: PPVI increased ROT-induced SH-SY5Y cell viability and improved ROT-induced cellular morphological changes. PPVI ameliorated ROT-induced oxidative stress status, and attenuated mitochondrial function and morphological changes. PPVI may exert neuroprotective effects through FOXO3 alpha/CREB1/DJ-1-related signaling pathways. Conclusion: These preliminary findings suggested that PPVI possesses neuroprotective attributes in vitro, and it may be a potential candidate for PD treatment. However, extensive research is necessary to fully understand the mechanisms of PPVI and its effectiveness both in vitro and in vivo.