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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2011-6-24
pubmed:abstractText
Linarin, a natural occurring flavanol glycoside derived from Mentha arvensis and Buddleja davidii is known to have anti-acetylcholinesterase effects. The present study intended to explore the neuroprotective effects of linarin against A?(25-35)-induced neurotoxicity with cultured rat pheochromocytoma cells (PC12 cells) and the possible mechanisms involved. For this purpose, PC12 cells were cultured and exposed to 30 ?M A?(25-35) in the absence or presence of linarin (0.1, 1.0 and 10 ?M). In addition, the potential contribution of the PI3K/Akt neuroprotective pathway in linarin-mediated protection against A?(25-35)-induced neurotoxicity was also investigated. The results showed that linarin dose-dependently increased cell viability and reduced the number of apoptotic cells as measured by MTT assay, Annexin-V/PI staining, JC-1 staining and caspase-3 activity assay. Linarin could also inhibit acetylcholinesterase activity induced by A?(25-35) in PC12 cells. Further study revealed that linarin induced the phosphorylation of Akt dose-dependently. Treatment of PC12 cells with the PI3K inhibitor LY294002 attenuated the protective effects of linarin. Furthermore, linarin also stimulated phosphorylation of glycogen synthase kinase-3? (GSK-3?), a downstream target of PI3K/Akt. Moreover, the expression of the anti-apoptotic protein Bcl-2 was also increased by linarin treatment. These results suggest that linarin prevents A?(25-35)-induced neurotoxicity through the activation of PI3K/Akt, which subsequently inhibits GSK-3? and up-regulates Bcl-2. These findings raise the possibility that linarin may be a potent therapeutic compound against Alzheimer's disease acting through both acetylcholinesterase inhibition and neuroprotection.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1464-3391
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4021-7
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Neuroprotective effects of linarin through activation of the PI3K/Akt pathway in amyloid-?-induced neuronal cell death.
pubmed:affiliation
Department of Pharmacology, School of Medicine, Shandong University, Shandong, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't