Abstract

Inhibition of beta-amyloid (A beta) accumulation and A beta fibril (fA beta) formation from A beta are attractive therapeutic targets for the treatment of Alzheimer's disease (AD). While previous studies have shown anti-amyloidogenic effects of curcumin in vitro and in vivo, no studies have examined optimized turmeric extracts enriched in curcuminoids or turmerones. Three standardized turmeric extracts, HSS-838, HSS-848, and HSS-888, were prepared with different chemical profiles to investigate their potential therapeutic benefits for AD. These extracts were fingerprinted by DART TOF-MS to reveal the significant chemical complexity. In addition four curcuminoids (curcumin, tetrahydrocurcumin, demethoxycurcumin and bisdemethoxycurcumin) were also examined. We measured the effects of the extracts and curcuminoids, on the aggregation of A beta by using a thioflavin T cell-free assay and the secretion of A beta from human neuronal cells (SweAPP N2A cells) in vitro. All three extracts and the curcuminoids showed dose-dependent inhibition of fA beta aggregation from A beta(1-42) in the cell-free assay, with IC(50) values of <or= 5 microg/mL. However, only HSS-888, curcumin and demethoxycurcumin significantly decreased A beta secretion (approximately 20%) in SweAPP N2A cells. Interaction matrices were used to examine possible synergistic interactions between HS-888 and the other extracts and the individual curcuminoids on A beta aggregation. Only simple additive effects were observed for the A beta aggregation inhibition, supporting the notion that the known curcuminoids are not strong inhibitors of this activity. However, HSS-888 showed strong inhibition of A beta aggregation and secretion, thus indicating that there are novel bioactive molecules in this extract that might be important leads for future AD drug discovery efforts.