- 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
- Copyright © 2022 Jayatunga, Hone, Fernando, Garg, Verdile and Martins. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Language
- eng
- Full Text
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