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This study examines the antioxidant capacity of papaya leaf extract (CPL) and its efficacy in reducing oxidative stress and inflammation in neuronal cells, which are key factors in neurodegenerative diseases. Through high-performance liquid chromatography coupled with diode-array detection, we quantified phenolic compounds present in CPL. Molecular docking analyses demonstrated strong binding affinities of these phenolics to proteins involved in antioxidant, anti-inflammatory, and anti-apoptotic pathways. Functionally, CPL and its active compounds reduced intracellular reactive oxygen species levels, upregulated Nrf-2/HO-1 expression, and decreased cytotoxicity in SH-SY5Y cells. Additionally, they downregulated apoptotic and inflammatory markers, highlighting its potential to modulate cellular response to oxidative stress. Furthermore, the neuroprotective effects of CPL and Vicenin-2 were significantly reduced by the Nrf-2 inhibitor, confirming their dependence on Nrf-2 signaling. These findings suggest that CPL holds significant potential as a neuroprotective agent, offering valuable insights into its mechanisms and highlighting its potential application in the prevention of neurodegenerative diseases.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s10068-025-01873-4.