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Assessment of diets containing curcumin, epigallocatechin-3-gallate, docosahexaenoic acid and α-lipoic acid on amyloid load and inflammation in a male transgenic mouse model of Alzheimer's disease: Are combinations more effective?

Sharman, MJ ORCID: 0000-0003-1005-4793, Gyengesi, E, Liang, H, Chatterjee, P, Karl, T, Li, Q-X, Wenk, MR, Halliwell, B, Martins, RN and Munch, G 2019 , 'Assessment of diets containing curcumin, epigallocatechin-3-gallate, docosahexaenoic acid and α-lipoic acid on amyloid load and inflammation in a male transgenic mouse model of Alzheimer's disease: Are combinations more effective?' , Neurobiology of Disease, vol. 124 , pp. 505-519 , doi: 10.1016/j.nbd.2018.11.026.

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Abstract

Increasingly, evidence is accumulating pointing at a protective role of a healthy diet at decreasing the risk of Alzheimer's disease. To test the effectiveness of nutritional components, the following food-derived compounds: curcumin alone (curcumin), curcumin combined with (-)epigallocatechin-3-gallate (EGCG), docosahexaenoic acid (DHA) and α-lipoic acid (ALA) (curcumin + EDA), or a combination of EGCG, DHA and ALA (EDA) were assessed in male Tg2576 transgenic mice on amyloid plaque load, amyloid levels (Aβ40/Aβ42, but not oligomers due to tissue limitations), microglial activation and memory using the contextual and cued fear conditioning test. The combination diet EDA, resulted in the strongest reduction of amyloid plaque load in both the cortical (p p β40/Aβ42 levels in the frontal cortex (p = .000129 and p = .000039, respectively) and Aβ42 levels in the temporal lobe (p = .000082). A curcumin only diet was shown to lower amyloid plaque load (p = .028), but when combined with EGCG, DHA and ALA did not result in further decreases in amyloid plaque load. The EDA combination group showed the most prominent decrease in microglial activation (number of microglia around plaques: p p p p = .001) spent increased time on freezing compared to the control group. In addition, the curcumin+EDA group showed a significant increase in time spent freezing compared with the curcumin only group. In the amygdala associated cued test, all mice demonstrated the ability to associate the conditioned stimulus with the unconditioned stimulus as evidenced by a significant increase in freezing behaviour in response to the presentation of the cue (p p p freezing during the cue presentation. The results from this study show that the combination of EGCG, DHA and ALA (EDA) appeared to have the most potent anti-inflammatory and neuroprotective effect. Our results also demonstrate that interactions between nutraceutical products might result in counterproductive outcomes, highlighting the fact that manufacturers of nutraceuticals containing multiple compounds should be careful not to claim additive or synergistic effects of their combination products in vivo without having tested it in animal models and/or human clinical trials.

Item Type: Article
Authors/Creators:Sharman, MJ and Gyengesi, E and Liang, H and Chatterjee, P and Karl, T and Li, Q-X and Wenk, MR and Halliwell, B and Martins, RN and Munch, G
Keywords: curcumin, microglia, amyloid plaque, inflammation, lipoic acid, green tea, fish oil
Journal or Publication Title: Neurobiology of Disease
Publisher: Academic Press Inc Elsevier Science
ISSN: 0969-9961
DOI / ID Number: 10.1016/j.nbd.2018.11.026
Copyright Information:

Copyright 2018 Published by Elsevier Inc.

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