Omics approaches to investigate the neuroprotective capacity of a Citrus sinensis (sweet orange) extract in a Caenorhabditis elegans Alzheimer's model.

Citrus sinensis by-products are a promising source of neuroprotective molecules. In this study, a pressurized liquid extract of Citrus by-products (PLE100) has been extensively characterized, and its neuroprotective capacity tested in the Caenorhabditis elegans strain CL4176, a validated in vivo model of Alzheimer's disease (AD). More than 450 compounds have been annotated in the extract, being triacylglycerols (TGs), stigmastanes, fatty acids (FAs) and carbohydrates the most abundant. The results demonstrate that worms PLE100-treated are significantly protected in a dose-dependent manner against the Aβ-peptide paralysis toxicity. The RNA-Seq data showed an alteration of 294 genes mainly related to the stress response defense along with genes involved in the lipid transport and metabolism. Moreover, the comprehensive metabolomics study allowed the identification of 818 intracellular metabolites, of which 54 were significantly altered (mainly lipids). The integration of these and previous results provides with new evidences of the protection mechanisms of this promising extract.