title: Optimized turmeric extracts have potent anti-amyloidogenic effects.
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.
authors.affiliation: Center for Excellence in Aging and Brain Repair, Department of Neurosurgery, University of South Florida College of Medicine, Tampa, FL 33612, USA.
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Shytle
authors.forename: Paula C
authors.initials: PC
authors.lastname: Bickford
authors.forename: Kavon
authors.initials: K
authors.lastname: Rezai-zadeh
authors.forename: L
authors.initials: L
authors.lastname: Hou
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
authors.forename: Cyndy D
authors.initials: CD
authors.lastname: Sanberg
authors.forename: Bill
authors.initials: B
authors.lastname: Roschek
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Fink
authors.forename: Randall S
authors.initials: RS
authors.lastname: Alberte
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D017077:Culture Media, Conditioned; D030024:Curcuma; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D036381:Diarylheptanoids; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D013058:Mass Spectrometry; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D017077:Culture Media, Conditioned; D036381:Diarylheptanoids; D010936:Plant Extracts; C096277:tetrahydrocurcumin; C012596:turmeric extract; D003474:Curcumin; C050229:demethoxycurcumin