EFE-8c4, a polyamine from Elaeagnus multiflora, protects neuronal cells by regulating oxidative stress and apoptotic pathways

Neurological disorders, including depression, cognitive impairment, and neurodegenerative diseases, are closely associated with oxidative stress, apoptotic neuronal loss, and impaired neuronal differentiation. Polyamine derivatives from natural products have emerged as potential neuroprotective agents, although their mechanisms remain incompletely understood. In this study, three polyamine compounds isolated from Elaeagnus multiflora fruit were evaluated in SH-SY5Y cell models of oxidative and glucocorticoid-induced stress. Among these, EFE-8c4 exhibited the most pronounced neuroprotective activity, significantly restoring cell viability under corticosterone-induced stress and attenuating oxidative damage induced by hydrogen peroxide. Mechanistically, EFE-8c4 modulated apoptotic signaling by increasing Bcl-2 expression while suppressing Bax, caspase-8, and p53 activation, thereby restoring the balance between pro- and anti-apoptotic pathways. In addition, EFE-8c4 reduced intracellular reactive oxygen species accumulation and enhanced the expression of PCNA and βIII-tubulin, indicating improved cell survival capacity and neuronal phenotype maintenance. Furthermore, EFE-8c4 partially reduced apoptotic cell populations under corticosterone exposure. Collectively, these findings demonstrate that EFE-8c4 exerts multi-target neuroprotective effects through coordinated regulation of apoptosis, oxidative stress, and neuronal differentiation-related pathways, highlighting its potential as a candidate for the treatment of oxidative stress-associated neurological disorders.