A Multilevel Study of Eupatorin and Scutellarein as Anti-Amyloid Agents in Alzheimers Disease

Today, Alzheimer ' s disease (AD)-the most common neurodegenerative disorder, which affects 50 million people-remains incurable. Several studies suggest that one of the main pathological hallmarks of AD is the accumulation of abnormal amyloid beta (A beta) aggregates; therefore, many therapeutic approaches focus on anti-A beta aggregation inhibitors. Taking into consideration that plantderived secondary metabolites seem to have neuroprotective effects, we attempted to assess the effects of two flavones-eupatorin and scutellarein-on the amyloidogenesis of A beta peptides. Biophysical experimental methods were employed to inspect the aggregation process of A beta after its incubation with each natural product, while we monitored their interactions with the oligomerized A beta through molecular dynamics simulations. More importantly, we validated our in vitro and in silico results in a multicellular organismal model-namely, Caenorhabditis elegans-and we concluded that eupatorin is indeed able to delay the amyloidogenesis of A beta peptides in a concentration-dependent manner. Finally, we propose that further investigation could lead to the exploitation of eupatorin or its analogues as potential drug candidates.