Neuroprotective Effects and Mechanisms of Arecoline Against H₂O₂-Induced Damage in SH-SY5Y Cells

An overproduction of reactive oxygen species (ROS) creates oxidative stress that disrupts neuronal activity and contributes to the pathogenesis of neurodegenerative diseases. Arecoline, the predominant alkaloid component of Areca catechu L., is known for multiple biological activities, yet its involvement in neuronal oxidative injury has not been fully clarified. This study investigated arecoline's effect on hydrogen peroxide (H₂O₂)-induced toxicity in SH-SY5Y human neuroblastoma cells (SH-SY5Y). Arecoline pretreatment significantly improved cell viability and preserved plasma membrane integrity, accompanied by reduced lipid peroxidation and restoration of cellular antioxidant enzyme activities. Moreover, arecoline maintained mitochondrial membrane potential and suppressed apoptotic progression. At the molecular level, Arecoline stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expression, concurrently diminishing Kelch-like ECH-associated protein 1 (Keap1) levels. In parallel, it altered the apoptosis profile by increasing B-cell lymphoma 2 (Bcl2) levels and decreasing Bcl-2-associated X protein (Bax) and total cysteine aspartate protease-3 (Caspase-3) protein expression. Collectively, the findings suggest that arecoline safeguards neurons against oxidative stress by simultaneously activating antioxidant defenses and restraining apoptosis. This study adds novel molecular evidence supporting the potential neuroprotective relevance of arecoline in oxidative stress-related neuropathology.