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.
Highlights
Plants, the immobile life on earth, have the inherent ability to synthesize defensive secondary metabolites, commonly known as phytochemicals, to withstand attacks by different organisms such as pathogens, insects, and herbivores
Combining natural compounds is popularizing in dealing with medical conditions where there is a shortage of discovery and approval of new drugs, and the existing monotherapies have shown limited therapeutic efficacy (Patti et al, 2017; Santana-Gálvez et al, 2019)
The combinations gave significantly higher ATP levels against the Aβ1-42-treated controls than the component compound concentrations (DHA, LUT, and urolithin A (UA) 5 μM each). These results suggest that pre-treatment with these combinations effectively attenuated Aβ1-42-induced toxicity
Summary
The immobile life on earth, have the inherent ability to synthesize defensive secondary metabolites, commonly known as phytochemicals, to withstand attacks by different organisms such as pathogens, insects, and herbivores. These phytochemicals have proven bioactivity through modulating molecular targets in living beings (Efferth and Koch, 2011). These bioactive phytochemicals are used in traditional medicine in China and Sri Lanka, and Ayurveda in India. Combining natural compounds is popularizing in dealing with medical conditions where there is a shortage of discovery and approval of new drugs, and the existing monotherapies have shown limited therapeutic efficacy (Patti et al, 2017; Santana-Gálvez et al, 2019)
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