RT Journal Article T1 Evaluation of the Protective Effects of Sarains on H2O2-Induced Mitochondrial Dysfunction and Oxidative Stress in SH-SY5Y Neuroblastoma Cells A1 Alvariño Romero, Rebeca A1 Alonso López, Eva A1 Tribalat, Marie-Aude A1 Gegunde Mosquera, Sandra A1 Thomas, Olivier P. A1 Botana López, Luis Miguel K1 Sarains K1 Oxidative stress K1 Nrf2 K1 mPTP K1 Cyclophilin D K1 Neuroprotection AB Sarains are diamide alkaloids isolated from theMediterranean sponge Haliclona (Rhizoniera) sarai that havepreviously shown antibacterial, insecticidal and anti-foulingactivities. In this study, we examined for the first time theneuroprotective effects of sarains 1, 2 and A against oxidativestress in a human neuronal model. SH-SY5Y cells were coincubated with sarains at concentrations ranging from 0.01 to10 μM, and the well-known oxidant hydrogen peroxide at150 μM for 6 h and the protective effects of the compoundswere evaluated. Among the sarains tested, sarain A was themost promising compound, improving mitochondrial functionand decreasing reactive oxygen species levels in human neuroblastoma cells treated with the compound at 0.01, 0.1 and1 μM. This compound was also able to increase the activity ofthe antioxidant enzymes superoxide dismutases by inducingthe translocation of the nuclear factor E2-related factor 2(Nrf2) to the nucleus at the lower concentrations tested (0.01and 0.1 μM). Moreover, sarain A at 0.1 and 1 μM blocked themitochondrial permeability transition pore (mPTP) openingthrough cyclophilin D inhibition. These results suggest thatthe protective effects produced by the treatment with sarainA are related with its ability to block the mPTP and to enhancethe Nrf2 pathway, indicating that sarain A may be a candidatecompound for further studies in neurodegenerative diseases PB Springer YR 2017 FD 2017 LK http://hdl.handle.net/10347/31614 UL http://hdl.handle.net/10347/31614 LA eng NO Alvariño, R., Alonso, E., Tribalat, MA. et al. Evaluation of the Protective Effects of Sarains on H2O2-Induced Mitochondrial Dysfunction and Oxidative Stress in SH-SY5Y Neuroblastoma Cells. Neurotox Res 32, 368–380 (2017) NO The research leading to these results has receivedfunding from the following FEDER cofunded-grants. From CDTI andTechnological Funds, supported by Ministerio de Economía, Industria yCompetitividad, AGL2014-58210-R, AGL2016-78728-R (AEI/FEDER,UE), ISCIII/PI16/01830 and RTC-2016-5507-2. From CDTI under ISIPProgramme, Spain, IDI-20130304 APTAFOOD and ITC-20161072.From the European Union’s Seventh Framework Programme managedby REA – Research Executive Agency (FP7/2007-2013) under grantagreement 312184 PHARMASEA DS Minerva RD 23 abr 2026