In vitro, in vivo, and in silico evidence for the use of plant pigments betalains as potential nutraceuticals against Alzheimer's disease

Abstract

Anti‐amyloidogenic properties of plant pigments betalains as potential nutraceuticals against Alzheimer's disease have been screened using 24 pure molecules. Twenty‐two betalains reduced amyloid aggregation in vitro, eight of them up to 100%, with IC50 values in the micromolar range. Atomic force and transmission electron microscopy images showed the typical fibrils associated with Alzheimer's disease and how betalains avoid its formation. Neuroprotection after ingestion was supported by in vivo experiments with Caenorhabditis elegans. Indoline‐betacyanin was the most effective molecule by significantly improving the chemotactic behavior of the CL2355 strain, a model of Alzheimer's disease. Furthermore, in‐depth molecular docking analyses revealed that the pigments interact with the N‐terminal region of the amyloid peptide. This work is the most comprehensive study in the field and provides in vitro, in vivo, and in silico evidence for the use of betalains as nutraceuticals of relevance in the prevention of Alzheimer's disease.