An Olive-Derived Extract 20% Rich in Hydroxytyrosol Prevents β-Amyloid Aggregation and Oxidative Stress, Two Features of Alzheimer Disease, via SKN-1/NRF2 and HSP-16.2 in Caenorhabditis elegans

Olive milling produces olive oil and different by-products, all of them very rich in different bioactive compounds like the phenolic alcohol hydroxytyrosol. The aim of the present study was to investigate the effects of an olive fruit extract 20% rich in hydroxytyrosol on the molecular mechanisms associated with Alzheimer disease features like A beta- and tau- induced toxicity, as well as on oxidative stress in Caenorhabditis elegans. Moreover, characterization of the extracts, regarding the profile and content of phenolics, as well as total antioxidant ability, was investigated. The study of lethality, growth, pharyngeal pumping, and longevity in vivo demonstrated the lack of toxicity of the extract. One hundred mu g/mL of extract treatment revealed prevention of oxidative stress and a delay in A beta-induced paralysis related with a lower presence of A beta aggregates. Indeed, the extract showed the ability to avoid a certain degree of proteotoxicity associated with aggregation of the tau protein. According to RNAi tests, SKN-1/NRF2 transcription factor and the overexpression of HSP-16.2 were mechanistically associated in the observed effects.

Automated summary

This study investigated the effects of an olive fruit extract rich in hydroxytyrosol on Alzheimer disease features using Caenorhabditis elegans model. The extract showed antioxidant properties and delayed Aβ-induced paralysis, and the observed effects were mechanistically associated with the regulation of SKN-1/NRF2 transcription factor and the overexpression of HSP-16.2.