Chronic stress in the central nervous system can lead to neurological dysfunction characterized by spontaneous neuronal cell death. This study investigated the neuroprotective potential of an aqueous extract of Lilium lancifolium Thunberg (ELL) against corticosterone (CORT)-induced pathophysiology in PC12 cells. To assess the neuroprotective effects of ELL, PC12 cells were pretreated with 50 µg/mL of ELL before being exposed to CORT. ELL significantly prevented CORT-induced neuronal cell death by attenuating pro-apoptotic protein expression, lactate dehydrogenase release, and reactive oxygen species generation, while maintaining intact adenosine triphosphate levels. Furthermore, ELL significantly mitigated CORT-induced endoplasmic reticulum (ER) stress responses by attenuating the elevation of unfolded protein responses, intracellular calcium levels, opening of mitochondrial permeability transition pores, and loss of mitochondrial membrane potential. In conclusion, ELL exerts neuroprotective effects by inhibiting apoptosis through the mitigation of CORT-induced ER stress and mitochondrial dysfunction, suggesting that ELL may prevent neuronal damage associated with chronic stress-induced neurotoxicity.
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