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?

Matthew J. Sharman, Erika Gyengesi, Huazheng Liang, Pratishtha Chatterjee, Tim Karl, Qiao Xin Li, Markus R. Wenk, Barry Halliwell, Ralph N. Martins, Gerald Münch

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2 Citations (Scopus)

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 Aβ 40 /Aβ 42 levels in the frontal cortex (p =.000129 and p =.000039, respectively) and Aβ 42 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.

Original languageEnglish
Pages (from-to)505-519
Number of pages15
JournalNeurobiology of Disease
Volume124
DOIs
Publication statusPublished - 1 Apr 2019

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Thioctic Acid
Curcumin
Docosahexaenoic Acids
Amyloid
Transgenic Mice
Alzheimer Disease
Diet
Inflammation
Amyloid Plaques
Freezing
Dietary Supplements
Fear
Cues
epigallocatechin gallate
Aptitude
Microglia
Frontal Lobe
Neuroprotective Agents
Temporal Lobe
Amygdala

Cite this

Sharman, Matthew J. ; Gyengesi, Erika ; Liang, Huazheng ; Chatterjee, Pratishtha ; Karl, Tim ; Li, Qiao Xin ; Wenk, Markus R. ; Halliwell, Barry ; Martins, Ralph N. ; Münch, Gerald. / 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?. In: Neurobiology of Disease. 2019 ; Vol. 124. pp. 505-519.
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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, Matthew J.; Gyengesi, Erika; Liang, Huazheng; Chatterjee, Pratishtha; Karl, Tim; Li, Qiao Xin; Wenk, Markus R.; Halliwell, Barry; Martins, Ralph N.; Münch, Gerald.

In: Neurobiology of Disease, Vol. 124, 01.04.2019, p. 505-519.

Research output: Contribution to journalArticle

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