Polyphenols from traditional Chinese medicine and Mediterranean diet are effective against Aβ toxicity in vitro and in vivo in Caenorhabditis elegans

The potential of naturally occurring polyphenols as nutraceuticals to prevent and/or treat Alzheimer's disease is studied. Five structurally related flavones and four tyrosols were tested in vitro in human amyloid-β peptide aggregation assays. The most promising compounds were two flavones, scutellarein and baicalein, and two tyrosols hydroxytyrosol and hydroxytyrosol acetate. These compounds caused a dose-dependent reduction of Aβ-peptide aggregation up to 90% for the flavones and 100% for the tyrosols, at concentrations of 83.3 μM and 33.3 mM, respectively. The IC50 value obtained for scutellarein was 22.5 μM, and was slightly higher for baicalein, 25.9 μM, while for hydroxytyrosol and hydroxytyrosol acetate they were 0.57 mM and 0.62 mM. Given these results, the compounds were selected to conduct in vivo assays with the Caenorhabditis elegans animal model of Alzheimer's disease. The amyloid anti-aggregation ability of these polyphenols was demonstrated in in vivo aggregation assays in which 1 mM hydroxytyrosol reduced the amyloid plaques in the mutant strain CL2331 by 43%. The neuroprotective effect was evaluated in chemotaxis experiments carried out with transgenic strain CL2355 that expresses the human amyloid-β peptide in the neurons. The chemotaxis index was improved by 240% when the neuron-impaired animals were treated with 1 mM hydroxytyrosol. The results indicate that the four molecules would be viable candidates to develop nutraceuticals that interfere in amyloid-β peptide aggregation and, consequently, prevent and/or treat Alzheimer's disease.