Studies On Anti?neuroinflammatory Mechanism Of Seleno-polymannuronate

Alginate is an acidic linear macromolecule with relatively high solubility from brown seaweeds,consisting ofβ-D-mannuronate（M）and its C-5 epimer,α-L-guluronate（G）.Selenium is an essential biological trace elelment and is found to have various biological activities.Seleno-polymannuronate（Se-PM）is a derivative from polymannuronate（PM）by the synthesis reaction.Microglia and astrocytes are the key factors of immune defense in the brain at normal physiological condition.Since microglia-or astrocyte-mediated neuroinflammation accelerates neuron damage and is critical for the induction of neurodegeneration due to lipopolysaccharide（LPS）.The effect and corresponding molecular mechanisms of Se-PM on the LPS-induced neuroinflammation in the BV2 cells,primary murine microglia and primary murine astrocytes were investigated in this study.And the LPS-stimulated acute inflammation mouse model were established for in vivo study.Se-PM obviously attenuated the LPS-induced production of nitric oxide（NO）,prostaglandin E₂（PGE₂）,tumor necrosis factor（TNF）-α,interleukin（IL）-1βand IL-6,as well as decreased the LPS-stimulated mRNA and protein expression of inducible nitric oxide synthase（iNOS）and cyclooxygenase 2（COX-2）in BV2 microglial cells dose-dependently,in primary microglia and in primary astrocytes.Additionally,Se-PM decreased the LPS-induced cellular morphological changes and migration in BV2 cells.Moreover,Se-PM could remarkably inhibit the LPS-stimulated activation of nuclear factor（NF）-κB and mitogen-activated protein kinase（MAPK）signalling pathways in BV2 cells,primary microglia and primary astrocytes.In vivo,Se-PM could attenuate LPS-induced acute inflammatory responses in mouse model by blocking the over-activation of microglia and astrocytes and by decreasing the secretion of TNF-αand IL-6 in the cerebral cortex.These findings indicate that Se-PM inhibits the neuroinflammation by blocking LPS-activated NF-κB and MAPK signalling pathways and reducing the excessive production of inflammatory mediators in microglia and astrocytes.It might be helpful to the development of nutraceuticals or drug for preventing the neuroinflammatory diseases.