This study investigated the neuroprotective activity of oligomeric stilbenes (OSs) derived from Alpha grape stems in various in vitro models of Parkinson’s disease (PD). Using neurotoxin-induced cellular models, including 1-methyl-4-phenylpyridine (MPP+), paraquat (PQ), 6-hydroxydopamine (6-OHDA), and rotenone, we screened the cytoprotective effects of ampelopsin A (1), ε-viniferin (2), vitisin D (3), vitisin A (4), α-viniferin (5), trans-vitisin B (6), cis-vitisin B (7), and melanoxylin A (8). The results demonstrate that certain stilbenes significantly enhanced cell viability and reduced reactive oxygen species (ROS) levels in neurotoxin-treated Neuro-2a cells. Notably, vitisin A and trans-vitisin B exhibited promising neuroprotective properties by decreasing mitochondrial ROS and cardiolipin peroxidation. This study highlights the potential of these compounds in mitigating oxidative stress and inflammation associated with PD. Additionally, we provided new insights into the antioxidant mechanisms of these stilbenes, including their direct ROS-scavenging abilities. Our findings contribute to the understanding of oligomeric stilbenes as potential therapeutic agents for the prevention and treatment of neurodegenerative diseases, particularly those associated with oxidative damage. Further research is warranted to explore its clinical applications and underlying mechanisms of action.
