A synergistic combination of DHA, luteolin, and urolithin A against Alzheimer’s disease

Authors

Dona P.W. Jayatunga, Edith Cowan University
Eugene Hone, Edith Cowan UniversityFollow
Binosha W.M.A. Fernando, Edith Cowan UniversityFollow
Manohar L. Garg
Giuseppe Verdile, Edith Cowan UniversityFollow
Ralph N. Martins, Edith Cowan UniversityFollow

Author Identifier

Dona P.W. Jayatunga

https://orcid.org/0000-0002-1386-5789

Giuseppe Verdile

https://orcid.org/0000-0003-2475-0124

Ralph N. Martins

https://orcid.org/0000-0002-4828-9363

Document Type

Journal Article

Publication Title

Frontiers in Aging Neuroscience

Volume

14

Publisher

Frontiers

School

School of Medical and Health Sciences / Centre of Excellence for Alzheimer's Disease Research and Care

RAS ID

45461

Funders

Edith Cowan University

Comments

Jayatunga, D. P., Hone, E., Fernando, W. B., Garg, M. L., Verdile, G., & Martins, R. N. (2022). A synergistic combination of DHA, luteolin, and urolithin a against Alzheimer’s disease. Frontiers in Aging Neuroscience, 14, Article 780602. https://doi.org/10.3389/fnagi.2022.780602

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 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.

DOI

10.3389/fnagi.2022.780602

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.