Alvariño Romero, RebecaAlonso López, EvaTribalat, Marie-AudeGegunde Mosquera, SandraThomas, Olivier P.Botana López, Luis Miguel2023-12-202023-12-202017Alvariño, 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)http://hdl.handle.net/10347/31614Sarains are diamide alkaloids isolated from the Mediterranean sponge Haliclona (Rhizoniera) sarai that have previously shown antibacterial, insecticidal and anti-fouling activities. In this study, we examined for the first time the neuroprotective effects of sarains 1, 2 and A against oxidative stress in a human neuronal model. SH-SY5Y cells were coincubated with sarains at concentrations ranging from 0.01 to 10 μM, and the well-known oxidant hydrogen peroxide at 150 μM for 6 h and the protective effects of the compounds were evaluated. Among the sarains tested, sarain A was the most promising compound, improving mitochondrial function and decreasing reactive oxygen species levels in human neuroblastoma cells treated with the compound at 0.01, 0.1 and 1 μM. This compound was also able to increase the activity of the antioxidant enzymes superoxide dismutases by inducing the translocation of the nuclear factor E2-related factor 2 (Nrf2) to the nucleus at the lower concentrations tested (0.01 and 0.1 μM). Moreover, sarain A at 0.1 and 1 μM blocked the mitochondrial permeability transition pore (mPTP) opening through cyclophilin D inhibition. These results suggest that the protective effects produced by the treatment with sarain A are related with its ability to block the mPTP and to enhance the Nrf2 pathway, indicating that sarain A may be a candidate compound for further studies in neurodegenerative diseasesengAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/SarainsOxidative stressNrf2mPTPCyclophilin DNeuroprotectionjournal article10.1007/s12640-017-9748-31476-3524open access