Study of the potential neuroprotective effect of Dunaliella salina extract in SH-SY5Y cell model

Alzheimer’s disease (AD) is the most common form of dementia caused by a progressive loss of neurons from different regions of the brain. This multifactorial pathophysiology has been widely characterized by neuroinflammation, extensive oxidative damage, synaptic loss, and neuronal cell death. In this sense, the design of multi-target strategies to prevent or delay its progression is a challenging goal. In the present work, different in vitro assays including antioxidant, anti-inflammatory, and anti-cholinergic activities of a carotenoid-enriched extract from Dunaliella salina microalgae obtained by supercritical fluid extraction are studied. Moreover, its potential neuroprotective effect in the human neuron-like SH-SY5Y cell model against remarkable hallmarks of AD was also evaluated. In parallel, a comprehensive metabolomics study based on the use of charged-surface hybrid chromatography (CSH) and hydrophilic interaction liquid chromatography (HILIC) coupled to high-resolution tandem mass spectrometry (Q-TOF MS/MS) was applied to evaluate the effects of the extract on the metabolism of the treated cells. The use of advanced bioinformatics and statistical tools allowed the identification of more than 314 metabolites in SH-SY5Y cells, of which a great number of phosphatidylcholines, triacylglycerols, and fatty acids were significantly increased, while several phosphatidylglycerols were decreased, compared to controls. These lipidomic changes in cells along with the possible role exerted by carotenoids and other minor compounds on the cell membrane might explain the observed neuroprotective effect of the D. salina extract. However, future experiments using in vivo models to corroborate this hypothesis must be carried out.A.V. would like to acknowledge the Spanish Ministry of Science, Innovation and Universities for his “Juan de la Cierva” post-doctoral grant (IJC2018-037560-I). J.D.S-M. would like acknowledge the Ministry of Education for a FPU predoctoral grant FPU17/01876. Z.J.S.M. would like to acknowledge the University of Nariño (Colombia) for financial support. The authors would like to thank projects ABACUS (Algae for a Biomass Applied to the produCtion of added value compounds—funded by the Bio Based Industries Joint Undertaking under the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 745668) and AGL2017-89417-R (MINECO, Spain) for funding.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.Peer reviewe