Martínez Caballero, María AranzazuLópez Torres, BernardoMaximiliano Guerra, Jorge EnriqueMartínez Caballero, MartaMartínez Larrañaga, María RosaAres Lombán, IrmaAnadón Navarro, Arturo RamónPeteiro, CesarAymerich, TeresaCasal-Silva, AndreaCueto, Mercedes2025-08-262025-08-262025Martínez, M. A., Lopez-Torres, B., Maximiliano, J. E., Martínez, M., Martínez-Larrañaga, M. R., Ares, I., Anadón, A., Peteiro, C., Aymerich, T., Casal-Silva, A., & Cueto, M. (2025). Eleganolone, a diterpene isolated from seaweed Bifurcaria bifurcata (Phaeophyceae, Fucales), protects neuronal cells from oxidative stress-induced damage. European journal of pharmacology, 1003, 177977. https://doi.org/10.1016/j.ejphar.2025.1779770014-299910.1016/j.ejphar.2025.177977https://hdl.handle.net/20.500.14352/123411Credit authorship contribution statement María-Aranzazu ´ Martínez: Writing – original draft, Validation, Methodology, Investigation, Funding acquisition, Formal analysis, Conceptualization. Bernardo Lopez-Torres: Validation, Methodology, Investigation, Formal analysis. Jorge-Enrique Maximiliano: Validation, Methodology, Investigation, Formal analysis. Marta Martínez: Validation, Methodology, Investigation, Formal analysis. María-Rosa Martínez-Larranaga: ˜ Validation, Methodology, Investigation, Formal analysis. Irma Ares: Writing – review & editing, Writing – original draft, Supervision, Investigation, Conceptualization. Arturo Anadon: ´ Writing – review & editing, Writing – original draft, Supervision, Investigation, Conceptualization. Cesar Peteiro: Writing – original draft, Investigation, Conceptualization. Teresa Aymerich: Methodology, Investigation, Funding acquisition, Conceptualization. Andrea Casal-Silva: Methodology, Investigation. Mercedes Cueto: Methodology, Investigation, ConceptualizationThe brown seaweed Bifurcaria bifurcata has gained particular interest in recent years due to its abundance in bioactive linear diterpenes with potential high-value applications. Evidences suggests that oxidative stress is an important mediator of neurodegenerative disorders. In this research study, the aim was to evaluate the potential protective effect of eleganolone, diterpene isolated from the brown seaweed B. bifurcata, on oxidative stressed human neuroblastoma SH-SY5Y cells by tert-butyl hydroperoxide (tert-BOOH). The protective effects of eleganolone on the oxidative stressed SH-SY5Y cells were measured by cell viability, cytotoxicity, oxidative stress biomarkers and antioxidative enzyme activity assays, as well as associated intracellular signaling pathways. The mRNA expression of apoptosis, inflammation, oxidative stress and neuronal development signaling pathway-related genes was analyzed by real-time RT-PCR. Eleganolone prevented the elevation of oxidative stress markers, such as reactive oxygen species, malondialdehyde, nitric oxide and caspase 3/7 activity, as well as induced an increase in reduced glutathione and antioxidant enzyme activities in a dose-dependent manner on oxidative stressed SH-SY5Y cells. Additionally, our data showed that eleganolone downregulated the expression of genes associated with apoptosis (BAX, BNIP3, p53, p38, APAF1), inflammation (NFKB1, TNF-α, IL-6, IL-1β), oxidative stress (HO-1) and neuronal development (CAMK2A, WNT5A, WNT7A) pathways in SH-SY5Y cells exposed to oxidative stressor tert-BOOH. These findings suggest that eleganolone offers neuroprotective potential in ameliorating diverse pathological aspects associated with oxidative stress.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article1879-0712https://doi.org/10.1016/j.ejphar.2025.17797740691930open access581.1Brown seaweed Bifurcaria bifurcataEleganoloneNeuroprotectionOxidative stressSH-SY5Y cellsFisiología vegetal (Farmacia)2417.19 Fisiología Vegetal