Structure-activity relationship of sulfated hetero/galactofucan polysaccharides on dopaminergic neuron.
Parkinson's disease (PD) is associated with progressive loss of dopaminergic neurons and more-widespread neuronal changes that cause complex symptoms. 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 DF2 could reverse the decreased mitochondrial activity and the increased LDL release induced by MPP(+) (P<0.01 or P<0.001) 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.
Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Nantong Branch, Institute of Oceanology, Chinese Academy of Sciences, Nantong, Jiangsu 226006, PR China.
Jing
J
Wang
School of Life Sciences, Nantong University, Seyuan Road 9, Nantong 226019, PR China.
Huaide
H
Liu
Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China.
Weihua
W
Jin
Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China.
Hong
H
Zhang
Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Nantong Branch, Institute of Oceanology, Chinese Academy of Sciences, Nantong, Jiangsu 226006, PR China. Electronic address: qbzhang@qdio.ac.cn.
Quanbin
Q
Zhang
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation; D006719:Homovanillic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D018384:Oxidative Stress; D011134:Polysaccharides / Q000737:chemistry* / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013329:Structure-Activity Relationship; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000975:Antioxidants; D018696:Neuroprotective Agents; D011134:Polysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C007789:fucoidan; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid
Neuron protection; Sulfated galactofucan polysaccharides; Sulfated hetero-polysaccharides