Solanum nigrum L. Extract Decreases Parkinsonism‐Induced Oxidative Neurodegeneration Through the Inhibition of TRPM2 Channel

Parkinson’s disease is caused by the 1‐methyl‐4‐phenylpyridinium (MPP)‐induced stimulation of the TRPM2 channel and the generation of free reactive oxygen species (ROS). The stimulation in SH‐SY5Y neuronal cells may be suppressed by the antioxidant Solanum nigrum L. (SNL) extract and TRPM2 antagonist (N‐(p‐amylcinnamoyl) anthranilic acid, ACA). The antioxidant and anti‐apoptotic properties of SNL were investigated in Parkinsonism (MPP)‐induced dopaminergic SH‐SY5Y cells by reducing the TRPM2 signaling molecular pathways. Four primary groups of SH‐SY5Y cells were generated: control (CNT), SNL (12.5 μg/mL for 24 h), MPP (0.5 mM for 6 h), and MPP + SNL. TRPM2 current density, cytosolic cation (Ca 2+ , Fe 2+ , and Zn 2+ ) concentrations, and the cell death percentage were increased due to the MPP incubation. MPP reduced antioxidants (glutathione peroxidase and glutathione) and cell viability while increasing apoptotic (caspases‐3, ‐8, and ‐9) and oxidant (lipid peroxidation, mitochondrial membrane dysfunction, and ROS) indicators. These indicators were further elevated by TRPM2 stimulation, although they were attenuated through TRPM2 inhibition by the treatment of SNL and ACA. In conclusion, the antioxidant property of SNL incubation decreased MPP‐induced mitochondrial oxidative cytotoxicity and cell death by blocking TRPM2‐mediated Ca 2+ signaling. SNL is a potential treatment for MPP‐induced Parkinsonism associated with excessive ROS generation, apoptosis, and Ca 2+ influx.