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Structure-activity relationship of sulfated hetero-polysaccharides and sulfated galactofucan polysaccharides on protective effect of dopaminergic neuron in vivo and in vitro

Jing Wang  Huaide Liu  Weihua Jin  Hong Zhang  Quanbin Zhang  
【摘要】:Parkinson disease(PD)is associated with progressive loss of dopaminergic neurons and more-widespread neuronal changes that cause complex symptoms.In the previous study,we had found fucoidan had neuron protective activity.We also found the fucoidan activity had relationship with their molecular weight,monosaccharides,uronic acid and sulfated group,however,the chemical-activity relationship on neuron protective activity is still unknown.We had found the low molecular weight fucoidan had better activity on renal protective activity and different fucoidan fractions exerted different activity,the low molecular weight galactofucan polysaccharides(DF2)showed best renal protective activity.Are the molecular weight and monosaccharide had effective on the neuron protective activity?Which sample had the strongest activity,Fucoidan(FPS),low molecular weight fucoidan(DF),or the low molecular weight fucoidan fractions(DFl and DF2)?The aim of this study was to investigate the structure-activity relationship of sulfated hetero-polysaccharides(DF1)and sulfated galactofucan polysaccharides(DF2)on dopaminergic neuron in vivo and in vitro.Treatment with samples significantly ameliorated the depletion of both DA and TH-,Bcl-2-and Bax-positive neurons in MPTP-induced PD mice,DF1 showed the highest activity.The in vitro results found that DF1 and DF2could reverse the decreased mitochondrial activity and the increased LDL release induced by MPP+(P0.01 or P0.001)which provides further evidence that DF1 and DF2 also exerts a direct protection against the neuronal injury caused by MPP~+.Furthermore,the administration of samples effectively decreased lipid peroxidation and increased the level/activities of GSH,GSH-PX,MDA and CAT in MPTP mice.Thus,the neuron protective effect may be mediated,in part,through antioxidant activity and the prevention of cell apoptosis.The chemical composition of DF1,DF2 and DF differed markedly,the DF1 fraction had the most complex chemical composition and showed the highest neuron protective activity.These results suggest that diverse monosaccharides and uronic acid might contribute to neuron protective activity.

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