| Summary: | Abstract In this study, an exhaustive chemical characterization of a Dunaliella salina (DS) microalga extract obtained using supercritical fluids has been performed, and its neuroprotective capacity has been evaluated in vivo using an Alzheimer’s disease (AD) transgenic model of Caenorhabditis elegans (strain CL4176). More than 350 compounds were annotated in the studied DS extract, with triacylglycerols, free fatty acids (FAs), carotenoids, apocarotenoids and glycerol being the most abundant. DS extract significantly protects C. elegans in a dose-dependent manner against Aβ-peptide paralysis toxicity, after 32 h, 53% of treated worms at 50 µg/mL were not paralyzed. This concentration was selected to further evaluate the transcriptomics and metabolomics changes after 26 h by using advanced analytical methodologies. The RNA-Seq data showed an alteration of 150 genes, mainly related to the stress and detoxification responses, and the retinol and lipid metabolism. The comprehensive metabolomics and lipidomics analyses allowed the identification of 793 intracellular metabolites, of which 69 were significantly altered compared to non-treated control animals. Among them, different unsaturated FAs, lysophosphatidylethanolamines, nucleosides, dipeptides and modified amino acids that have been previously reported as beneficial during AD progression, were assigned. These compounds could explain the neuroprotective capacity observed, thus, providing with new evidences of the protection mechanisms of this promising extract.
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