title: Treatment of a multiple sclerosis animal model by a novel nanodrop formulation of a natural antioxidant.
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.
authors.affiliation: Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Orli
authors.initials: O
authors.lastname: Binyamin
authors.affiliation: Casali Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Liraz
authors.initials: L
authors.lastname: Larush
authors.affiliation: Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Kati
authors.initials: K
authors.lastname: Frid
authors.affiliation: Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Guy
authors.initials: G
authors.lastname: Keller
authors.affiliation: Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Friedman-Levi
authors.affiliation: Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Haim
authors.initials: H
authors.lastname: Ovadia
authors.affiliation: Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Oded
authors.initials: O
authors.lastname: Abramsky
authors.affiliation: Casali Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Shlomo
authors.initials: S
authors.lastname: Magdassi
authors.affiliation: Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Gabizon
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008315:Malondialdehyde / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry*; D010084:Oxidation-Reduction; D010316:Particle Size; D010938:Plant Oils / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008055:Lipids; D010938:Plant Oils; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde
keywords: EAE; PSO; nanodrops; neurodegeneration; oxidative stress