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Neuroprotective effects of linarin through activation of the PI3K/Akt pathway in amyloid-β-induced neuronal cell death.
Bioorg Med Chem. 2011 Jul 01; 19(13):4021-7.BM

Abstract

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 Aβ(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 μM Aβ(25-35) in the absence or presence of linarin (0.1, 1.0 and 10 μM). In addition, the potential contribution of the PI3K/Akt neuroprotective pathway in linarin-mediated protection against Aβ(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 Aβ(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-3β (GSK-3β), 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 Aβ(25-35)-induced neurotoxicity through the activation of PI3K/Akt, which subsequently inhibits GSK-3β 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.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine, Shandong University, Shandong, PR China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21652214

Citation

Lou, Haiyan, et al. "Neuroprotective Effects of Linarin Through Activation of the PI3K/Akt Pathway in Amyloid-β-induced Neuronal Cell Death." Bioorganic & Medicinal Chemistry, vol. 19, no. 13, 2011, pp. 4021-7.
Lou H, Fan P, Perez RG, et al. Neuroprotective effects of linarin through activation of the PI3K/Akt pathway in amyloid-β-induced neuronal cell death. Bioorg Med Chem. 2011;19(13):4021-7.
Lou, H., Fan, P., Perez, R. G., & Lou, H. (2011). Neuroprotective effects of linarin through activation of the PI3K/Akt pathway in amyloid-β-induced neuronal cell death. Bioorganic & Medicinal Chemistry, 19(13), 4021-7. https://doi.org/10.1016/j.bmc.2011.05.021
Lou H, et al. Neuroprotective Effects of Linarin Through Activation of the PI3K/Akt Pathway in Amyloid-β-induced Neuronal Cell Death. Bioorg Med Chem. 2011 Jul 1;19(13):4021-7. PubMed PMID: 21652214.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective effects of linarin through activation of the PI3K/Akt pathway in amyloid-β-induced neuronal cell death. AU - Lou,Haiyan, AU - Fan,Peihong, AU - Perez,Ruth G, AU - Lou,Hongxiang, Y1 - 2011/05/19/ PY - 2011/04/08/received PY - 2011/05/12/revised PY - 2011/05/13/accepted PY - 2011/6/10/entrez PY - 2011/6/10/pubmed PY - 2011/10/18/medline SP - 4021 EP - 7 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 19 IS - 13 N2 - 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 Aβ(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 μM Aβ(25-35) in the absence or presence of linarin (0.1, 1.0 and 10 μM). In addition, the potential contribution of the PI3K/Akt neuroprotective pathway in linarin-mediated protection against Aβ(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 Aβ(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-3β (GSK-3β), 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 Aβ(25-35)-induced neurotoxicity through the activation of PI3K/Akt, which subsequently inhibits GSK-3β 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. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/21652214/Neuroprotective_effects_of_linarin_through_activation_of_the_PI3K/Akt_pathway_in_amyloid_β_induced_neuronal_cell_death_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(11)00366-X DB - PRIME DP - Unbound Medicine ER -