Neuroprotective effects of ellagic acid on cuprizone-induced acute demyelination through limitation of microgliosis, adjustment of CXCL12/IL-17/IL-11 axis and restriction of mature oligodendrocytes apoptosis
Context: Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuropathologic conditions. Objective: In vivo neuroprotective effects of EA on cuprizone (cup)-induced demyelination were evaluated. Material and meth...
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| Main Authors: | , , , , , , , , , |
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| Format: | Book |
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Taylor & Francis Group,
2017-01-01T00:00:00Z.
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| Summary: | Context: Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuropathologic conditions. Objective: In vivo neuroprotective effects of EA on cuprizone (cup)-induced demyelination were evaluated. Material and methods: C57BL/6 J mice were fed with chow containing 0.2% cup for 4 weeks to induce oligodendrocytes (OLGs) depletion 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 cup diet. Oligodendrocytes apoptosis [TUNEL assay and myelin oligodendrocyte glycoprotein (MOG+)/caspase-3+ cells), gliosis (H&E staining, glial fibrillary acidic protein (GFAP+) and macrophage-3 (Mac-3+) cells) and inflammatory markers (interleukin 17 (IL-17), interleukin 11 (IL-11) and stromal cell-derived factor 1 α (SDF-1α) or CXCL12] during cup intoxication were examined. Results: High dose of EA (EA-80) increased mature oligodendrocytes population (MOG+ cells, p < 0.001), and decreased apoptosis (p < 0.05) compared with the cup mice. Treatment with both EA doses did not show any considerable effects on the expression of CXCL12, but significantly down-regulated the expression of IL-17 and up-regulated the expression of IL-11 in mRNA levels compared with the cup mice. Only treatment with EA-80 significantly decreased the population of active macrophage (MAC-3+ cells, p < 0.001) but not reactive astrocytes (GFAP+ cells) compared with the cup mice. Discussion and conclusion: In this model, EA-80 effectively reduces lesions via reduction of neuroinflammation and toxic effects of cup on mature OLGs. EA is a suitable therapeutic agent for moderate brain damage in neurodegenerative diseases such as multiple sclerosis. |
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| Item Description: | 1388-0209 1744-5116 10.1080/13880209.2017.1319867 |