Strawberry leaf extract protects dopaminergic neurons by restoring redox and mitochondrial homeostasis

Introduction Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons, for which effective disease-modifying strategies remain limited. Mitochondrial dysfunction and oxidative stress are central drivers of PD pathogenesis, highlighting the importance of cellular defense mechanisms targeting these processes. Methods In the present study, we investigated the neuroprotective effects of strawberry leaf extract (SLE), an agricultural by-product rich in polyphenols, using both in vitro and in vivo models of PD. Results In SH-SY5Y cells, SLE significantly attenuated rotenone-induced loss of cell viability and suppressed intracellular reactive oxygen species (ROS) production. Mechanistically, SLE promoted nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the expression of antioxidant genes, including heme oxygenase-1 (HO-1) and p62. Pharmacological inhibition experiments further indicated that activation of AMP-activated protein kinase (AMPK) contributes to SLE-induced Nrf2 activation. In addition to redox regulation, SLE modulated mitochondrial quality control pathways. Time-dependent alterations in mitophagy-related markers, including PINK1, Parkin, LC3, and p62, were observed, accompanied by recovery of mitochondrial membrane potential. These findings suggest that SLE influences mitochondrial homeostasis under oxidative stress conditions. In a rotenone-induced PD mouse model, SLE administration ameliorated motor dysfunction and attenuated the loss of tyrosine hydroxylase-positive dopaminergic neurons in the substantia nigra. Discussion Collectively, these results demonstrate that SLE exerts neuroprotective effects through coordinated regulation of the AMPK -Nrf2 signaling axis and mitochondrial quality control pathways. This study provides mechanistic insight into the potential of food-derived bioactive compounds as modulators of neurodegenerative processes and highlights SLE as a promising candidate for PD prevention or intervention.