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Optimized Turmeric Extracts have Potent Anti-Amyloidogenic Effects

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Inhibition of β-amyloid (Aβ) accumulation and Aβ fibril (fAβ) formation from Aβ 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 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.

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Keywords: Alzheimer's disease; DART TOF-MS; amyloid aggregation; amyloid secretion; curcuminoids; turmeric extracts

Document Type: Research Article

Publication date: December 1, 2009

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  • Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.
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