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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 in the prevention and treatment of EAE.Notes: Mice induced for EAE were administered Nano-PSO in two different start points. As shown in the insert, while one group of induced mice was left untreated (n=8), a second group was treated with Nano-PSO from day 1 of the induction (n=6) and a third group from day 7 of the induction (n=7). Mice were scored daily for EAE signs for 2 additional weeks. P<0.05 for both Nano-PSO treatments.Abbreviations: PSO, pomegranate seed oil; EAE, experimental autoimmune encephalomyelitis.
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f4-ijn-10-7165: Nano-PSO in the prevention and treatment of EAE.Notes: Mice induced for EAE were administered Nano-PSO in two different start points. As shown in the insert, while one group of induced mice was left untreated (n=8), a second group was treated with Nano-PSO from day 1 of the induction (n=6) and a third group from day 7 of the induction (n=7). Mice were scored daily for EAE signs for 2 additional weeks. P<0.05 for both Nano-PSO treatments.Abbreviations: PSO, pomegranate seed oil; EAE, experimental autoimmune encephalomyelitis.

Mentions: Next, we tested whether Nano-PSO can reduce neurological damage already inflicted by EAE induction, as opposed to prevent/delay EAE onset. To this effect, we compared the clinical effect of Nano-PSO administration from the day of induction (10 μL PSO/d) to that of the same dose administered from day 7 postinduction (graph results from day 10 postinduction). It is well established that at this time point of EAE induction, activated immune cells are already formed and infiltrated into the central nervous system (CNS).34Figure 4 shows that Nano-PSO administration exerts a beneficial effect at both time points (P<0.05); however, while the early treatment shows both delay in disease onset and reduced disease burden, the latter treatment only shows reduced scores but a similar kinetics of disease presentation as the untreated mice. This is a very encouraging result, indicating Nano-PSO could be beneficial to humans already suffering from early signs of demyelinating diseases such as MS.


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 in the prevention and treatment of EAE.Notes: Mice induced for EAE were administered Nano-PSO in two different start points. As shown in the insert, while one group of induced mice was left untreated (n=8), a second group was treated with Nano-PSO from day 1 of the induction (n=6) and a third group from day 7 of the induction (n=7). Mice were scored daily for EAE signs for 2 additional weeks. P<0.05 for both Nano-PSO treatments.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

f4-ijn-10-7165: Nano-PSO in the prevention and treatment of EAE.Notes: Mice induced for EAE were administered Nano-PSO in two different start points. As shown in the insert, while one group of induced mice was left untreated (n=8), a second group was treated with Nano-PSO from day 1 of the induction (n=6) and a third group from day 7 of the induction (n=7). Mice were scored daily for EAE signs for 2 additional weeks. P<0.05 for both Nano-PSO treatments.Abbreviations: PSO, pomegranate seed oil; EAE, experimental autoimmune encephalomyelitis.
Mentions: Next, we tested whether Nano-PSO can reduce neurological damage already inflicted by EAE induction, as opposed to prevent/delay EAE onset. To this effect, we compared the clinical effect of Nano-PSO administration from the day of induction (10 μL PSO/d) to that of the same dose administered from day 7 postinduction (graph results from day 10 postinduction). It is well established that at this time point of EAE induction, activated immune cells are already formed and infiltrated into the central nervous system (CNS).34Figure 4 shows that Nano-PSO administration exerts a beneficial effect at both time points (P<0.05); however, while the early treatment shows both delay in disease onset and reduced disease burden, the latter treatment only shows reduced scores but a similar kinetics of disease presentation as the untreated mice. This is a very encouraging result, indicating Nano-PSO could be beneficial to humans already suffering from early signs of demyelinating diseases such as MS.

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