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.