title: A polysaccharide from Polygonatum sibiricum attenuates amyloid-β-induced neurotoxicity in PC12 cells.
abstract: One of the pathological hallmarks of Alzheimer's disease (AD) is the progressive accumulation of beta-amyloid (Aβ) in the form of senile plaques, and Aβ induced neurotoxicity has been identified as a major cause of the onset of AD. In this study, we investigated the protective effects of a polysaccharide (PS-WNP) from Polygonatum sibiricum against the Aβ(25-35)-induced neurotoxicity in PC12 cells and explored the underlying mechanism. The results showed that pretreatment with PS-WNP significantly attenuated cell death and the elevated Bax/Bcl-2 ratio evoked by Aβ(25-35), and subsequently inhibited mitochondrial dysfunction and cytochrome c release into the cytosol. Moreover, PS-WNP significantly inhibited Aβ(25-35) induced caspase-3 activation and enhanced the protein levels of phosphorylated Akt (p-Akt) in PC12 cells. Additionally, pretreatment with the PI3K inhibitor (LY294002) completely abolished the protective effects of PS-WNP against Aβ(25-35)-induced neuronal cell apoptosis. These observations unambiguously suggested that the protective effect of PS-WNP against Aβ(25-35)-induced apoptosis in PC12 cells was associated with the enhancement of PI3K/Akt signaling pathway.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Huixue
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China; Department of Neurology, Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Yuze
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China. Electronic address: chenlixia_harbin@hotmail.com.
authors.forename: Lixia
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Piyun
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China. Electronic address: lh_wangchin@126.com.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D031384:Polygonatum / Q000737:chemistry*; D011134:Polysaccharides / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D027343:Rhizome / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D011134:Polysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3
keywords: Akt; Alzheimer's disease; Neuroprotection; PC12 cells; Polygonatum sibiricum; Polysaccharide