title: Ellagic acid ameliorates cuprizone-induced acute CNS inflammation via restriction of microgliosis and down-regulation of CCL2 and CCL3 pro-inflammatory chemokines.
abstract: Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuro-inflammatory conditions. Microglia making the innate immune system of the central nervous system (CNS) and are imperative cellular mediators of neuro-inflammatory processes. In this study, neuro-protective effects of EA on cuprizone (Cup)-induced acute CNS inflammation evaluated. C57BL/6J mice were fed with chow containing 0.2 % Cup for 3 weeks to induce acute neuro-inflammation predominantly in the corpus callosum (CC). EA was administered at different doses (40 or 80 mg/kg body weight/day/i.p) from the first day of the Cup diet. Microglia activation (microgliosis) and expression of microglia related chemokines during Cup challenge were examined. Results shows that EA significantly decreased the number of activated microglia cells (Iba-1+ cells) and also restricted proliferation of these cell population (Iba-1+/Ki67+ cells) in dose dependent manner. Consequently, concentration of microglial pro-inflammatory chemokines including monocyte chemoattractant protein-1/Chemokine (C-C motif) ligand 2 (MCP-1/CCL2), and macrophage inflammatory protein 1-alpha/Chemokine (C-C motif) ligand 3 (MIP-1-α/CCL3) dramatically reduced in CC after EA treatment. According to this results, we conclude that EA is a suitable therapeutic agent for moderation brain damages in neuro-inflammatory diseases.
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: N
authors.initials: N
authors.lastname: Sanadgol
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: F
authors.initials: F
authors.lastname: Golab
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. amostafaie@mbrc.ac.ir.
authors.forename: A
authors.initials: A
authors.lastname: Mostafaie
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Mehdizadeh
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Abdollahi
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Sharifzadeh
authors.affiliation: Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Ravan
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D054405:Chemokine CCL3 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism; D003471:Cuprizone / Q000633:toxicity; D015536:Down-Regulation / Q000187:drug effects*; D004610:Ellagic Acid / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008856:Microscopy, Fluorescence; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D008840:Microfilament Proteins; D004610:Ellagic Acid; D003471:Cuprizone; D053148:Caspase 3