Rosmarinic acid, a catechol-containing natural product, potently inhibits amylin amyloidosis

Epidemiological studies show significant association between obesity related type 2 diabetes (T2D) and risk for cerebrovascular disease and dementia (including Alzheimer’s disease, AD). Amylin is a peptide hormone whose high propensity to form amyloid in the pancreas contributes to TD2 pathology. Recently, heterologous amyloid composed of amylin and amyloid beta (the causative agent and amyloid forming species in AD) has also been found in the brain tissue of individuals with AD and T2D but not age matched healthy controls. Collectively these data suggest that amylin aggregation may represent a molecular link between AD and TD2. From a targeted screening of a collection of natural compounds used in complementary medicine, we identified that rosmarinic acid (RA) is a highly potent inhibitor against amylin amyloid formation (apparent IC50 estimated at 200 nM). Further characterization indicates that RA and its metabolites caffeic acid (CA) and salvianic acid A (SAA), exert additive anti-amylin aggregation a...