Protective effects of a nano-formulation of curcumin against cuprizone-induced demyelination in the mouse corpus callosum

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), characterized by neuroinflammation, oligodendrocytes (OLs) loss and demyelination Curcumin, a natural phenolic substance, has been shown to have significant therapeutic properties in various neurodegenerative diseases, including MS. In our laboratory by loading curcumin in dendrosome nanoparticles we improved its solubility and bioavailability. Our previous study showed anti-inflammatory and anti-oxidative effects of dendrosomal nano-curcumin (DNC) in experimental autoimmune encephalomyelitis (EAE) model of MS. Here, by using a toxic demyelination model, induced by cuprizone (CPZ), we investigated the protective effect of DNC on oligodendroglial lineage cells (OLLC) and myelin preservation in context of acute demyelination. CPZ is a copper chelator, thus its intake reduces the mitochondrial activity, activates oxidative stress response, leading to specific OLs death, due to their high-energy consumption. We also evaluated DNC effect on activation of astrocytes and microglia, which are enriched in both MS and CPZ demyelinated lesions. Our results demonstrated that DNC treatment protected OLLCs against CPZ toxin. Besides DNC treatment suppressed accumulation of astrocytes and microglia in CC of CPZ-fed mice, compared to PBS treated once. Moreover, DNC treatment led to higher index of luxal fast blue (LFB) and myelin-specific proteins, myelin basic protein (MBP) intensity in the corpus callosum (CC), as indicators of myelin content. These results suggest a potent pleiotropic therapeutic efficiency for DNC for protection of myelinating cells, possibly via suppression of astrocytes and microglia