Optimized Turmeric Extracts have Potent Anti-Amyloidogenic Effects
R. Douglas Shytle,
Paula C. Bickford,
Paul R. Sanberg,
Cyndy D. Sanberg,
Bill Roschek Jr.,
Ryan C. Fink,
Randall S. Alberte.
Inhibition of β-amyloid (Aβ) accumulation and Aβ fibril (fAβ) formation from Aβ are attractive therapeutic targets for the treatment of Alzheimers 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 Aβ by using a thioflavin T cell-free assay and the secretion of Aβ from human neuronal cells (SweAPP N2A cells) in vitro. All three extracts and the curcuminoids showed dose-dependent inhibition of fAβ aggregation from Aβ1-42 in the cell-free assay, with IC50 values of 5 μÊg/mL. However, only HSS-888, curcumin and demethoxycurcumin significantly decreased Aβ secretion (∼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 Aβ aggregation. Only simple additive effects were observed for the Aβ aggregation inhibition, supporting the notion that the known curcuminoids are not strong inhibitors of this activity. However, HSS-888 showed strong inhibition of Aβ 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.
Keywords: Alzheimer's disease, curcuminoids, turmeric extracts, amyloid aggregation, amyloid secretion, DART TOF-MS
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