RT Journal Article T1 Eleganolone, a diterpene isolated from seaweed Bifurcaria bifurcata (Phaeophyceae, Fucales), protects neuronal cells from oxidative stress-induced damage. A1 Martínez Caballero, María Aranzazu A1 López Torres, Bernardo A1 Maximiliano Guerra, Jorge Enrique A1 Martínez Caballero, Marta A1 Martínez Larrañaga, María Rosa A1 Ares Lombán, Irma A1 Anadón Navarro, Arturo Ramón A1 Peteiro, Cesar A1 Aymerich, Teresa A1 Casal-Silva, Andrea A1 Cueto, Mercedes AB The 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. PB Elsevier SN 0014-2999 YR 2025 FD 2025 LK https://hdl.handle.net/20.500.14352/123411 UL https://hdl.handle.net/20.500.14352/123411 LA eng NO Martínez, 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.2025.177977 NO Credit authorship contribution statementMaría-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, Conceptualization NO Ministerio de Ciencia e Innovacion y Universidades ( España) DS Docta Complutense RD 20 ene 2026