The neuroprotective effects of Chalcones from Ashitaba on cuprizone-induced demyelination via modulation of brain-derived neurotrophic factor and tumor necrosis factor α.

Abstract

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. However, the limitations of available therapeutic strategies are frustrating, both in terms of their low efficacy and multiple side effects. Previous studies showed that natural compounds such as Chalcones possess neuroprotective effects on neurodegenerative disorders. However, few studies have so far been published on the potential effects of Chalcones on treating demyelinating disease. The present study was designed to investigate the effects of Chalcones from Ashitaba (ChA) on cuprizone-induced noxious changes in the C57BL6 mice model of MS. The mice received normal diets (Control group: CNT), or Cuprizone-supplemented diets either without ChA (Cuprizone group: CPZ) or with low or high (300, 600mg/kg/day) doses of ChA (ChA-treated groups: CPZ+ChA300/600). Brain-derived neurotrophic factor (BDNF) and tumor necrosis factor alpha (TNFα) levels, demyelination scores in the corpus callosum (CC), and cognitive impairment were evaluated using the enzyme-linked immunosorbent assay, histological, and Y-maze tests, respectively. The findings showed that ChA Co-treatment significantly reduced the extent of demyelination in the CC and the serum and brain levels of TNFα in the ChA-treated groups compared to the CPZ group. Besides, treatment with a higher dose of ChA significantly improved the behavioral responses and BDNF levels in the serum and brain of the CPZ+ChA600 group when compared with the CPZ group. The present study provided evidence for the neuroprotective effects of ChA on cuprizone-induced demyelination and behavioral dysfunction in C57BL/6 mice, possibly by modulating TNFα secretion and BDNF expression.