Protective Effects of Wogonin against Alzheimer's Disease by Inhibition of Amyloidogenic Pathway

被引:30
作者
Huang, Ding-Siang [1 ]
Yu, Yu-Chen [1 ]
Wu, Chung-Hsin [1 ]
Lin, Jung-Yaw [1 ]
机构
[1] Natl Taiwan Normal Univ, Dept Life Sci, Taipei, Taiwan
关键词
CYTOCHROME-C RELEASE; A-BETA; OXIDATIVE STRESS; MITOCHONDRIAL DYSFUNCTION; FLAVONOID WOGONIN; MOUSE MODEL; ACTIVATION; MEMORY; CELLS; NEUROTOXICITY;
D O I
10.1155/2017/3545169
中图分类号
R [医药、卫生];
学科分类号
10 ;
摘要
One of the pathogenic systems of Alzheimer's disease (AD) is the formation of beta-amyloid plaques in the brains of patients, and amyloidogenic activity becomes one of the therapeutic targets. Here, we report wogonin, one of the major active constituting components in Scutellaria baicalensis, which has the neuroprotective effects on amyloid-beta peptides-(A beta-) induced toxicity. Oral wogonin treatment improved the performance of triple transgenic AD mice (h-APPswe, h-Tau P301L, and h-PS1 M146V) on the Morris water maze, Y-maze, and novel object recognition. Furthermore, wogonin activated the neurite outgrowth of AD cells by increasing neurite length and complexity of Tet-On A beta(42)-GFP SH-SY5Y neuroblastoma cells (AD cells) and attenuated amyloidogenic pathway by decreasing the levels of beta-secretase, APP beta-C-terminal fragment, A beta-aggregation, and phosphorylated Tau. Wogonin also increased mitochondrial membrane potential (Delta psi m) and protected against apoptosis by reducing the expression of Bax and cleaved PARP. Collectively, these results conclude that wogonin may be a promising multifunctional drug candidate for AD.
引用
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页数:13
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共 51 条
  • [31] Mufson Elliott J, 2008, Expert Rev Neurother, V8, P1703, DOI 10.1586/14737175.8.11.1703
  • [32] Triple-transgenic model of Alzheimer's disease with plaques and tangles:: Intracellular Aβ and synaptic dysfunction
    Oddo, S
    Caccamo, A
    Shepherd, JD
    Murphy, MP
    Golde, TE
    Kayed, R
    Metherate, R
    Mattson, MP
    Akbari, Y
    LaFerla, FM
    [J]. NEURON, 2003, 39 (03) : 409 - 421
  • [33] Structure-neurotoxicity relationships of amyloid β-protein oligomers
    Ono, Kenjiro
    Condron, Margaret M.
    Teplow, David B.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (35) : 14745 - 14750
  • [34] The Transient Receptor Potential Melastatin 2 (TRPM2) Channel Contributes to β-Amyloid Oligomer-Related Neurotoxicity and Memory Impairment
    Ostapchenko, Valeriy G.
    Chen, Megan
    Guzman, Monica S.
    Xie, Yu-Feng
    Lavine, Natalie
    Fan, Jue
    Beraldo, Flavio H.
    Martyn, Amanda C.
    Belrose, Jillian C.
    Mori, Yasuo
    MacDonald, John F.
    Prado, Vania F.
    Prado, Marco A. M.
    Jackson, Michael F.
    [J]. JOURNAL OF NEUROSCIENCE, 2015, 35 (45) : 15157 - 15169
  • [35] Bilirubin and amyloid-β peptide induce cytochrome c release through mitochondrial membrane permeabilization
    Rodrigues, CMP
    Solá, S
    Silva, R
    Brites, D
    [J]. MOLECULAR MEDICINE, 2000, 6 (11) : 936 - 946
  • [36] Synaptic memory mechanisms:: Alzheimer's disease amyloid β-peptide-induced dysfunction
    Rowan, M. J.
    Klyubin, I.
    Wang, Q.
    Hu, N. W.
    Anwyl, R.
    [J]. BIOCHEMICAL SOCIETY TRANSACTIONS, 2007, 35 : 1219 - 1223
  • [37] Bcl-2 family proteins as ion-channels
    Schendel, SL
    Montal, M
    Reed, JC
    [J]. CELL DEATH AND DIFFERENTIATION, 1998, 5 (05) : 372 - 380
  • [38] Deficiency of Neuronal p38α MAPK Attenuates Amyloid Pathology in Alzheimer Disease Mouse and Cell Models through Facilitating Lysosomal Degradation of BACE1
    Schnoeder, Laura
    Hao, Wenlin
    Qin, Yiren
    Liu, Shirong
    Tomic, Inge
    Liu, Xu
    Fassbender, Klaus
    Liu, Yang
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 291 (05) : 2067 - 2079
  • [39] Alzheimer's Disease
    Selkoe, Dennis J.
    [J]. COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2011, 3 (07): : 1 - 16
  • [40] In vitro mitochondrial failure and oxidative stress mimic biochemical features of Alzheimer disease
    Selvatici, Rita
    Marani, Luca
    Marino, Silvia
    Siniscalchi, Anna
    [J]. NEUROCHEMISTRY INTERNATIONAL, 2013, 63 (02) : 112 - 120