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Article Publish Status: FREE
Abstract Title:

A Synergistic Combination of DHA, Luteolin, and Urolithin A Against Alzheimer's Disease.

Abstract Source:

Front Aging Neurosci. 2022 ;14:780602. Epub 2022 Feb 16. PMID: 35250535

Abstract Author(s):

Dona P W Jayatunga, Eugene Hone, W M A D Binosha Fernando, Manohar L Garg, Giuseppe Verdile, Ralph N Martins

Article Affiliation:

Dona P W Jayatunga

Abstract:

Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the most common form of dementia worldwide. The classical AD brain is characterized by extracellular deposition of amyloid-β (Aβ) protein aggregates as senile plaques and intracellular neurofibrillary tangles (NFTs), composed of hyper-phosphorylated forms of the microtubule-associated protein Tau. There has been limited success in clinical trials for some proposed therapies for AD, so attention has been drawn toward using alternative approaches, including prevention strategies. As a result, nutraceuticals have become attractive compounds for their potential neuroprotective capabilities. The objective of the present study was to derive a synergistic nutraceutical combinationthat may act as a potential preventative therapy for AD. The compounds of interest were docosahexaenoic acid (DHA), luteolin (LUT), and urolithin A (UA). The cell viability and cytotoxicity assays MTS and LDH were used to evaluate the compounds individually and in two-compound combinations, for their ability to inhibit Aβ-induced toxicity in human neuroblastoma BE(2)-M17 cells. The LDH-derived% protection values were used in the program CompuSyn v.1.0 to calculate the combination index (CI) of the two-compound combinations. The software-predicted potentially synergistic (CI<1) two-compound combinations were validated using CellTiter Glo assay. Finally, a three-compound combination was predicted (DLU) and shown to be the most effective at inhibiting Aβ-induced toxicity. The synergistic combination, DLUwarrants further research for its mechanism of action; however, it can serve as a basis to develop an advanced functional food for the prevention or co-treatment of AD.

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