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Neurobiol Dis. 2019 Jan 2;124:505-519. doi: 10.1016/j.nbd.2018.11.026. [Epub ahead of print]

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?

Author information

1
School of Health Sciences, College of Health and Medicine, University of Tasmania, Locked Bag 1322, Launceston, TAS 7250, Australia.
2
School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia; Molecular Medicine Research Group, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia.
3
School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia.
4
Department of Biomedical Sciences, Macquarie University, North Ryde, NSW 2113, Australia; Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia.
5
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
6
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117456, Singapore; Department of Biological Sciences, National University of Singapore, 117543, Singapore.
7
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117456, Singapore.
8
Department of Biomedical Sciences, Macquarie University, North Ryde, NSW 2113, Australia; Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia; Sir James McCusker Alzheimer's disease Research Unit, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia 6009, Australia.
9
School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia; Molecular Medicine Research Group, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia; National Institute of Complementary Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW 2751, Australia. Electronic address: g.muench@westernsydney.edu.au.

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 < .0001) and hippocampal (p < .0001) areas of the Tg2576 mouse brain, along with lower Aβ40/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 < .05 and p < .0001, respectively, for the cortex and hippocampus). Analysing the hippocampal associated contextual fear conditioning revealed that both the curcumin+EDA (p < .0001) and EDA groups (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 < .0001). Post-hoc analysis showed that only curcumin+EDA (p < .0001) and EDA groups (p < .0001) developed a significant increase in 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.

KEYWORDS:

Amyloid plaque; Curcumin; Fish oil; Green tea; Inflammation; Lipoic acid; Microglia

PMID:
30610916
DOI:
10.1016/j.nbd.2018.11.026

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