- Title
- A Synergistic Combination of DHA, Luteolin, and Urolithin A Against Alzheimer’s Disease
- Creator
- Jayatunga, Dona P. W.; Hone, Eugene; Fernando, W. M. A. D. Binosha; Garg, Manohar L.; Verdile, Giuseppe; Martins, Ralph N.
- Relation
- Frontiers in Aging Neuroscience Vol. 14, Issue 16 February 2022, no. 780602
- Publisher Link
- http://dx.doi.org/10.3389/fnagi.2022.780602
- Publisher
- Frontiers Research Foundation
- Resource Type
- journal article
- Date
- 2022
- Description
- 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 combination in vitro that 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 Aβ1–42-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 (D5L5U5) and shown to be the most effective at inhibiting Aβ1–42-induced toxicity. The synergistic combination, D5L5U5 warrants 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.
- Subject
- Alzheimer’s disease; docosahexaenoic acid; in vitro; Luteolin; synergistic nutraceutical combinations; urolithin A; SGD 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1488584
- Identifier
- uon:52486
- Identifier
- ISSN:1663-4365
- Rights
- x
- Language
- eng
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