title: Neuroprotective effects of puerarin against beta-amyloid-induced neurotoxicity in PC12 cells via a PI3K-dependent signaling pathway.
abstract: Epidemiological data have indicated that estrogen replacement therapy (ERT) can decrease the risk of developing Alzheimer's disease (AD). Phytoestrogens have been proposed as potential alternatives to ERT. The aim of the present study was to assess the neuroprotective effects of puerarin, a phytoestrogen isolated from Pueraria lobata, against the toxicity of beta-amyloid (Aβ) in relation to the mitochondria-mediated cell death process, and to elucidate the role the activation of Akt and modulation of the pro- and antiapoptotic proteins in puerarin-induced neuroprotection. The present study shows that puerarin afforded protection against Aβ-induced toxicity through inhibiting apoptosis in PC12 cells. This result was also confirmed by the activated caspase-3 assay. P-Akt, Bcl-2 and p-Bad expression increased after pretreatment with puerarin in PC12 cells exposed to Aβ(25-35), whereas Bax expression and cytochrome c release decreased. Interestingly, these effects of puerarin against Aβ(25-35) insult were abolished by wortmannin, an inhibitor of PI3K phosphorylation. These findings suggest that puerarin prevent Aβ-induced neurotoxicity through inhibiting neuronal apoptosis, and might be a potential preventive or therapeutic agent for AD.
authors.affiliation: The Institute of Medicine, Qiqihar Medical University, 333 BuKui Street, JianHua District, Qiqihar 161042, China.
authors.forename: Guihua
authors.initials: G
authors.lastname: Xing
authors.forename: Miaoxian
authors.initials: M
authors.lastname: Dong
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Zou
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Defu
authors.initials: D
authors.lastname: Cai
authors.forename: Chengchong
authors.initials: C
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Jicheng
authors.initials: J
authors.lastname: Liu
authors.forename: Yingcai
authors.initials: Y
authors.lastname: Niu
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D018709:Statistics, Nonparametric; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D017304:Annexin A5; D004791:Enzyme Inhibitors; D007529:Isoflavones; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D013778:Tetrazolium Salts; D013844:Thiazoles; C074636:amyloid beta-protein (25-35); D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; C022616:thiazolyl blue; C033607:puerarin