Original Article
Pomegranate seed oil nanoemulsions for the prevention and treatment of neurodegenerative diseases: the case of genetic CJD

https://doi.org/10.1016/j.nano.2014.03.015Get rights and content

Abstract

Neurodegenerative diseases generate the accumulation of specific misfolded proteins, such as PrPSc prions or A-beta in Alzheimer's diseases, and share common pathological features, like neuronal death and oxidative damage. To test whether reduced oxidation alters disease manifestation, we treated TgMHu2ME199K mice, modeling for genetic prion disease, with Nano-PSO, a nanodroplet formulation of pomegranate seed oil (PSO). PSO comprises large concentrations of a unique polyunsaturated fatty acid, Punicic acid, among the strongest natural antioxidants. Nano-PSO significantly delayed disease presentation when administered to asymptomatic TgMHu2ME199K mice and postponed disease aggravation in already sick mice. Analysis of brain samples revealed that Nano-PSO treatment did not decrease PrPSc accumulation, but rather reduced lipid oxidation and neuronal loss, indicating a strong neuroprotective effect. We propose that Nano-PSO and alike formulations may be both beneficial and safe enough to be administered for long years to subjects at risk or to those already affected by neurodegenerative conditions.

From the Clinical Editor

This team of authors report that a nanoformulation of pomegranade seed oil, containing high levels of a strong antioxidant, can delay disease onset in a mouse model of genetic prion diseases, and the formulation also indicates a direct neuroprotective effect.

Graphic abstract

In this work, we administered to transgenic mice mimicking a genetic prion disease, which develop a late onset fatal disease, a nanoemulsions formulation of pomegranate seed oil, denominated Nano-PSO. We show in the manuscript that this formulation is successful in inhibiting disease onset when given to still asymptomatic mice and disease progression when given to already sick mice. Nano-PSO treatment reduced brain lipid oxidation and other key neurodegeneration features.

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Section snippets

Animal experiments

All animal experiments were conducted under the guidelines and supervision of the Hebrew University Ethical Committee, which approved of the methods employed in this project (Permit Number: MD-11746-5).

Treatment of TgMHu2ME199K mice

PSO and Nano-PSO were administrated to TgMHu2ME199K mice modeling for E200K CJD expressing human-mouse chimeric E199K PrP on a null (for homozygous) or a wt PrP (for heterozygous) background,23 as described in Table 2. In the PSO experiments,1, 2, 3 mouse pelleted feed to which PSO was added as

Delay of disease onset following administration of PSO in food to young and asymptomatic TgMHu2ME199K mice

Groups of asymptomatic TgMHu2ME199K mice (TgMHu2ME199K/wt and TgMHu2ME199K/KO),23 as well as 7 months old TgMHu2ME199K/KO mice already presenting significant neurological signs (see Table 1 for description of disease scores, and Table 2 for details about the experimental groups) were fed either with regular rodent food or with food enriched with pomegranate seed oil (PSO) at a concentration of 25 ml oil/kg. Since mice consume about 3-4 g of food/day, we may assume treated mice received about 100 μl

Discussion

A significant number of natural anti-oxidants are ubiquitously present in a healthy human diet. Many of them, such as Sulforaphane from Broccoli, Curcumin and EGCG from green tea were recognized for their neuroprotective properties in cells and tested in appropriate animal models.64, 65, 66 However, their in vivo activity was limited by the sub-pharmacological doses presented in food, their poor bioavailability to humans, rapid chemical degradation and reduced distribution to different organs

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    Funding: This project was funded by a grant from the Israel Science Foundation (ISF) and by the Agnes Ginges Center. At present time, a commercial entity (Granalix) is being formed based on the presented results

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    Equal contribution.

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