RT Journal Article
T1 Neuroprotective effects of furanoditerpenes from Spongia (Spongia) tubulifera through cyclophilin D modulation against ischemia/reperfusion injury in BV2 microglial cells
A1 Castedo Caldeiro, Noelia
A1 Alfonso Rancaño, María Amparo
A1 Alvariño Romero, Rebeca
A1 Pech-Puch, Dawrin
A1 Ageitos Castiñeiras, Lucía
A1 Rodríguez González, Jaime
A1 Rodríguez Vieytes, Mercedes
A1 Jiménez González, Carlos
A1 Botana López, Luis Miguel
K1 Cyclophilin D
K1 Furanoditerpenes
K1 Inflammation
K1 Ischemia
K1 Microglia
AB Ischemia induces oxidative stress and mitochondrial dysfunction in microglia, contributing to neuro-inflammation and neuronal damage. Five furanoditerpenes 1–5, isolated from the marine sponge Spongia (Spongia) tubulifera, have previously shown neuroprotective effects related to their capacity to bind cyclophilin D (CypD), a protein involved in ischemia. In this study, the ability of compounds 1–5 to alleviate ischemic damage was evaluated on BV2 microglial cells. First, cells were incubated under oxygen deprivation for 6 h, and the five compounds were able to improve cell viability at micromolar concentrations (0.001–1 μM). Then, hypoxia was combined with the inflammatory stimulus lipopolysaccharide and with glucose deprivation, and Spongia tubulifera metabolites maintained their protective effects. When oxygen and glucose deprivation was followed by 6 h of reperfusion, compounds 1–5 also mitigated the damage produced on microglia. Moreover, these furanoditerpenes reduced reactive oxygen species overproduction and restored mitochondrial membrane potential, key factors in ischemic damage. This effect was mediated by the regulation of CypD since compounds 2, 4, and 5 reduced its expression under ischemia conditions. Finally, trans-well coculture experiments were performed between microglial and SH-SY5Y neuronal cells. In this assay, compounds 2, 4, and 5 protected neuronal cells from microglial-induced neurotoxicity under ischemia/reperfusion conditions. These findings suggest that S. tubulifera metabolites display mitochondrial-mediated antioxidant and cytoprotective effects under ischemic conditions through CypD modulation. Given the limitations of current Cyps inhibitors like cyclosporin A, compounds 1–5 are promising therapeutic candidates for ischemia-related diseases, such as stroke
PB American Chemical Society
SN 1948-7193
YR 2026
FD 2026-03-11
LK https://hdl.handle.net/10347/46638
UL https://hdl.handle.net/10347/46638
LA eng
NO Castedo, N., Alfonso, A., Alvariño, R., Pech-Puch, D., Ageitos, L., Rodríguez, J., Vieytes, M. R., Jiménez, C., & Botana, L. M. (2026). Neuroprotective Effects of Furanoditerpenes from Spongia (Spongia) Tubulifera through Cyclophilin D Modulation against Ischemia/Reperfusion Injury in BV2 Microglial Cells. ACS chemical neuroscience, 17(7), 1332–1344. https://doi.org/10.1021/acschemneuro.5c00949
NO The research leading to these results has received funding from the following grants: Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, GRC (GI-1682-2025); Ministerio de Ciencia e Innovación, Grant CPP2021-008447 funded by MCIN/AEI/10.13039/501100011033 and by The European Union NextGeneration EU/PRT; Ministerio de Ciencia, Innovación y Universidades, PID2023-149618OB-I00; European Union Interreg EAPA-0032/2022─BEAP-MAR, and EAPA_0130/2024─REVALGAE (cofunded by the EU); and European Union HORIZON-CL6-2023-CIRCBIO-01 COMBO─101135438. N.C. is funded by predoctoral Xunta de Galicia fellowship ED481A_2023.
DS Minerva
RD 23 abr 2026