title: AstragalusPolysaccharide Suppresses 6-Hydroxydopamine-Induced Neurotoxicity inCaenorhabditis elegans.
abstract: Astragalus membranaceusis a medicinal plant traditionally used in China for a variety of conditions, including inflammatory and neural diseases.Astragaluspolysaccharides are shown to reduce the adverse effect of levodopa which is used to treat Parkinson's disease (PD). However, the neuroprotective effect ofAstragaluspolysaccharidesper sein PD is lacking. UsingCaenorhabditis elegansmodels, we investigated the protective effect of astragalan, an acidic polysaccharide isolated fromA. membranaceus, against the neurotoxicity of 6-hydroxydopamine (6-OHDA), a neurotoxin that can induce parkinsonism. We show that 6-OHDA is able to degenerate dopaminergic neurons and lead to the deficiency of food-sensing behavior and a shorter lifespan inC. elegans. Interestingly, these degenerative symptoms can be attenuated by astragalan treatment. Astragalan is also shown to alleviate oxidative stress through reducing reactive oxygen species level and malondialdehyde content and increasing superoxide dismutase and glutathione peroxidase activities and reduce the expression of proapoptotic geneegl-1in 6-OHDA-intoxicated nematodes. Further studies reveal that astragalan is capable of elevating the decreased acetylcholinesterase activity induced by 6-OHDA. Together, our results demonstrate that the protective effect of astragalan against 6-OHDA neurotoxicity is likely due to the alleviation of oxidative stress and regulation of apoptosis pathway and cholinergic system and thus provide an important insight into the therapeutic potential ofAstragaluspolysaccharide in neurodegeneration.
authors.affiliation: Center for Bioresources & Drug Discovery and School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Bioresources & Drug Discovery and School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Ruona
authors.identifier: 0000-0001-8500-3769
authors.initials: R
authors.lastname: Shi
authors.affiliation: Center for Bioresources & Drug Discovery and School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ding
authors.affiliation: Center for Bioresources & Drug Discovery and School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Center for Bioresources & Drug Discovery and School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Han
authors.affiliation: Research & Development Center, Infinitus (China) Company Ltd., Guangzhou 510665, China.
authors.forename: Fangli
authors.initials: F
authors.lastname: Ma
authors.affiliation: Research & Development Center, Infinitus (China) Company Ltd., Guangzhou 510665, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Hu
authors.affiliation: Research & Development Center, Infinitus (China) Company Ltd., Guangzhou 510665, China.
authors.forename: Chung Wah
authors.initials: CW
authors.lastname: Ma
authors.affiliation: Center for Bioresources & Drug Discovery and School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Zebo
authors.identifier: 0000-0003-2431-3741
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D027885:Astragalus propinquus / Q000737:chemistry*; D001522:Behavior, Animal / Q000187:drug effects; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D044949:Kaempferols / Q000302:isolation & purification / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008136:Longevity / Q000187:drug effects; D009410:Nerve Degeneration; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine; D008517:Phytotherapy; D010946:Plants, Medicinal; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; C112486:EGL-1 protein, C elegans; D044949:Kaempferols; D018696:Neuroprotective Agents; D011134:Polysaccharides; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D016627:Oxidopamine; C001579:astragalin; D000110:Acetylcholinesterase