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Treatment of a multiple sclerosis animal model by a novel nanodrop formulation of a natural antioxidant.

Binyamin O, Larush L, Frid K, Keller G, Friedman-Levi Y, Ovadia H, Abramsky O, Magdassi S, Gabizon R - Int J Nanomedicine (2015)

Bottom Line: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and is associated with demyelination, neurodegeneration, and sensitivity to oxidative stress.Pathological examinations revealed that Nano-PSO administration dramatically reduced demyelination and oxidation of lipids in the brains of the affected animals, which are hallmarks of this severe neurological disease.On the mechanistic side, our results demonstrate that lipid oxidation may be a seminal feature in both demyelination and neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.

ABSTRACT
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and is associated with demyelination, neurodegeneration, and sensitivity to oxidative stress. In this work, we administered a nanodroplet formulation of pomegranate seed oil (PSO), denominated Nano-PSO, to mice induced for experimental autoimmune encephalomyelitis (EAE), an established model of MS. PSO comprises high levels of punicic acid, a unique polyunsaturated fatty acid considered as one of the strongest natural antioxidants. We show here that while EAE-induced mice treated with natural PSO presented some reduction in disease burden, this beneficial effect increased significantly when EAE mice were treated with Nano-PSO of specific size nanodroplets at much lower concentrations of the oil. Pathological examinations revealed that Nano-PSO administration dramatically reduced demyelination and oxidation of lipids in the brains of the affected animals, which are hallmarks of this severe neurological disease. We propose that novel formulations of natural antioxidants such as Nano-PSO may be considered for the treatment of patients suffering from demyelinating diseases. On the mechanistic side, our results demonstrate that lipid oxidation may be a seminal feature in both demyelination and neurodegeneration.

No MeSH data available.


Related in: MedlinePlus

Nano-PSO as an α-EAE agent.Notes: Mice were induced for EAE and treated from day 1 of the induction either with PSO or with Nano-PSO. (A) Designated EAE-induced groups were fed either with normal mouse chow (untreated group; n=10) or with chow enriched with PSO at the concentration in which 3 g (daily intake) comprises the levels designated in the figure insert: 100 (n=10) or 300 μL (n=8) PSO. P<0.05 for all PSO-treated groups versus the untreated group. (B) Designated EAE-induced groups were either left untreated or treated (by gavage) with 150 μL solution comprising 0.2, 0.8 (n=6), or 10 μL (n=7) PSO in the form of Nano-PSO. P<0.05 for 0.8 and 10 μL PSO-treated group versus the untreated group.Abbreviations: PSO, pomegranate seed oil; EAE, experimental autoimmune encephalomyelitis.
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f2-ijn-10-7165: Nano-PSO as an α-EAE agent.Notes: Mice were induced for EAE and treated from day 1 of the induction either with PSO or with Nano-PSO. (A) Designated EAE-induced groups were fed either with normal mouse chow (untreated group; n=10) or with chow enriched with PSO at the concentration in which 3 g (daily intake) comprises the levels designated in the figure insert: 100 (n=10) or 300 μL (n=8) PSO. P<0.05 for all PSO-treated groups versus the untreated group. (B) Designated EAE-induced groups were either left untreated or treated (by gavage) with 150 μL solution comprising 0.2, 0.8 (n=6), or 10 μL (n=7) PSO in the form of Nano-PSO. P<0.05 for 0.8 and 10 μL PSO-treated group versus the untreated group.Abbreviations: PSO, pomegranate seed oil; EAE, experimental autoimmune encephalomyelitis.

Mentions: To induce EAE, groups of C57Bl naïve female mice were immunized with an emulsion comprising MOG35–55 peptide and complete Freund’s adjuvant, resulting in an acute neurological paralytic disease followed by partial remission.32,33 Following the induction, mice were scored daily for disease signs as described in the “Materials and methods” section. Figure 2A shows results from an experiment in which EAE-induced mice were fed from the day of induction either with normal chow (untreated) or with chow to which increasing concentrations of PSO (see levels of oil in graph legend) were added per 3 g of chow, which is the average daily consumption of food by each mouse. The figure shows that daily doses of 100–300 μL of PSO were effective in reducing disease burden in the EAE mice (60% of the highest score in the EAE untreated mice for the 100 μL PSO dose and 36% for the 300 μL dose; P<0.05 for PSO-treated groups versus untreated groups). Lower levels of PSO were not effective against the disease. While this constitutes a proof of principle that high levels of PSO can have an anti-EAE effect, such levels of oil, in particular when converted to human doses (4–12 mL of oil/d), are difficult to consume on a daily basis.


Treatment of a multiple sclerosis animal model by a novel nanodrop formulation of a natural antioxidant.

Binyamin O, Larush L, Frid K, Keller G, Friedman-Levi Y, Ovadia H, Abramsky O, Magdassi S, Gabizon R - Int J Nanomedicine (2015)

Nano-PSO as an α-EAE agent.Notes: Mice were induced for EAE and treated from day 1 of the induction either with PSO or with Nano-PSO. (A) Designated EAE-induced groups were fed either with normal mouse chow (untreated group; n=10) or with chow enriched with PSO at the concentration in which 3 g (daily intake) comprises the levels designated in the figure insert: 100 (n=10) or 300 μL (n=8) PSO. P<0.05 for all PSO-treated groups versus the untreated group. (B) Designated EAE-induced groups were either left untreated or treated (by gavage) with 150 μL solution comprising 0.2, 0.8 (n=6), or 10 μL (n=7) PSO in the form of Nano-PSO. P<0.05 for 0.8 and 10 μL PSO-treated group versus the untreated group.Abbreviations: PSO, pomegranate seed oil; EAE, experimental autoimmune encephalomyelitis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664546&req=5

f2-ijn-10-7165: Nano-PSO as an α-EAE agent.Notes: Mice were induced for EAE and treated from day 1 of the induction either with PSO or with Nano-PSO. (A) Designated EAE-induced groups were fed either with normal mouse chow (untreated group; n=10) or with chow enriched with PSO at the concentration in which 3 g (daily intake) comprises the levels designated in the figure insert: 100 (n=10) or 300 μL (n=8) PSO. P<0.05 for all PSO-treated groups versus the untreated group. (B) Designated EAE-induced groups were either left untreated or treated (by gavage) with 150 μL solution comprising 0.2, 0.8 (n=6), or 10 μL (n=7) PSO in the form of Nano-PSO. P<0.05 for 0.8 and 10 μL PSO-treated group versus the untreated group.Abbreviations: PSO, pomegranate seed oil; EAE, experimental autoimmune encephalomyelitis.
Mentions: To induce EAE, groups of C57Bl naïve female mice were immunized with an emulsion comprising MOG35–55 peptide and complete Freund’s adjuvant, resulting in an acute neurological paralytic disease followed by partial remission.32,33 Following the induction, mice were scored daily for disease signs as described in the “Materials and methods” section. Figure 2A shows results from an experiment in which EAE-induced mice were fed from the day of induction either with normal chow (untreated) or with chow to which increasing concentrations of PSO (see levels of oil in graph legend) were added per 3 g of chow, which is the average daily consumption of food by each mouse. The figure shows that daily doses of 100–300 μL of PSO were effective in reducing disease burden in the EAE mice (60% of the highest score in the EAE untreated mice for the 100 μL PSO dose and 36% for the 300 μL dose; P<0.05 for PSO-treated groups versus untreated groups). Lower levels of PSO were not effective against the disease. While this constitutes a proof of principle that high levels of PSO can have an anti-EAE effect, such levels of oil, in particular when converted to human doses (4–12 mL of oil/d), are difficult to consume on a daily basis.

Bottom Line: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and is associated with demyelination, neurodegeneration, and sensitivity to oxidative stress.Pathological examinations revealed that Nano-PSO administration dramatically reduced demyelination and oxidation of lipids in the brains of the affected animals, which are hallmarks of this severe neurological disease.On the mechanistic side, our results demonstrate that lipid oxidation may be a seminal feature in both demyelination and neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.

ABSTRACT
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and is associated with demyelination, neurodegeneration, and sensitivity to oxidative stress. In this work, we administered a nanodroplet formulation of pomegranate seed oil (PSO), denominated Nano-PSO, to mice induced for experimental autoimmune encephalomyelitis (EAE), an established model of MS. PSO comprises high levels of punicic acid, a unique polyunsaturated fatty acid considered as one of the strongest natural antioxidants. We show here that while EAE-induced mice treated with natural PSO presented some reduction in disease burden, this beneficial effect increased significantly when EAE mice were treated with Nano-PSO of specific size nanodroplets at much lower concentrations of the oil. Pathological examinations revealed that Nano-PSO administration dramatically reduced demyelination and oxidation of lipids in the brains of the affected animals, which are hallmarks of this severe neurological disease. We propose that novel formulations of natural antioxidants such as Nano-PSO may be considered for the treatment of patients suffering from demyelinating diseases. On the mechanistic side, our results demonstrate that lipid oxidation may be a seminal feature in both demyelination and neurodegeneration.

No MeSH data available.


Related in: MedlinePlus