TY - JOUR
T1 - Neuroprotective effects of Biochanin A against β-amyloid-induced neurotoxicity in PC12 cells via a mitochondrial-dependent apoptosis pathway
AU - Tan, Ji Wei
AU - Kim, Min Kyu
N1 - Funding Information:
This research was supported by Research University Grant Scheme (RUGS 05-02-12-1860RU), University Putra Malaysia (UPM). Ji Wei Tan is a recipient of MyPhD scholarship under MyBrain15 programme.
Publisher Copyright:
© 2016 by the authors; licensee MDPI.
Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 2016/5
Y1 - 2016/5
N2 - Alzheimer's disease is considered one of the major neurodegenerative diseases and is characterized by the production of β- amyloid (Aβ) proteins and progressive loss of neurons. Biochanin A, a phytoestrogen compound found mainly in Trifolium pratense, was used in the present study as a potential alternative to estrogen replacement therapy via the investigation of its neuroprotective effects against Aβ25-35-induced toxicity, as well as of its potential mechanisms of action in PC12 cells. Exposure of these cells to the Aβ25-35 protein significantly increased cell viability loss and apoptosis. However, the effects induced by Aβ25-35 were markedly reversed in the present of biochanin A. Pretreatment with biochanin A attenuated the cytotoxic effect of the Aβ25-35 protein by decreasing viability loss, LDH release, and caspase activity in cells. Moreover, we found that expression of cytochrome c and Puma were reduced, alongside with the restoration of Bcl-2/Bax and Bcl-xL/Bax ratio in the presence of biochanin A, which led to a decrease in the apoptotic rate. These data demonstrate that mitochondria are involved in the protective effect of biochanin A against Aβ25-35 and that this drug attenuated Aβ25- 35-induced PC12 cell injury and apoptosis by preventing mitochondrial dysfunction. Thus, biochanin A might raise a possibility as a potential therapeutic agent for Alzheimer's disease and other related neurodegenerative diseases.
AB - Alzheimer's disease is considered one of the major neurodegenerative diseases and is characterized by the production of β- amyloid (Aβ) proteins and progressive loss of neurons. Biochanin A, a phytoestrogen compound found mainly in Trifolium pratense, was used in the present study as a potential alternative to estrogen replacement therapy via the investigation of its neuroprotective effects against Aβ25-35-induced toxicity, as well as of its potential mechanisms of action in PC12 cells. Exposure of these cells to the Aβ25-35 protein significantly increased cell viability loss and apoptosis. However, the effects induced by Aβ25-35 were markedly reversed in the present of biochanin A. Pretreatment with biochanin A attenuated the cytotoxic effect of the Aβ25-35 protein by decreasing viability loss, LDH release, and caspase activity in cells. Moreover, we found that expression of cytochrome c and Puma were reduced, alongside with the restoration of Bcl-2/Bax and Bcl-xL/Bax ratio in the presence of biochanin A, which led to a decrease in the apoptotic rate. These data demonstrate that mitochondria are involved in the protective effect of biochanin A against Aβ25-35 and that this drug attenuated Aβ25- 35-induced PC12 cell injury and apoptosis by preventing mitochondrial dysfunction. Thus, biochanin A might raise a possibility as a potential therapeutic agent for Alzheimer's disease and other related neurodegenerative diseases.
KW - Alzheimer's disease
KW - Apoptosis
KW - Beta-amyloid
KW - Biochanin A
KW - Mitochondrial dysfunction
KW - PC12 cells
UR - http://www.scopus.com/inward/record.url?scp=84973661613&partnerID=8YFLogxK
U2 - 10.3390/molecules21050548
DO - 10.3390/molecules21050548
M3 - Article
C2 - 27120593
AN - SCOPUS:84973661613
VL - 21
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 5
M1 - 548
ER -