Neuroprotective Effects of Biochanin A against β-Amyloid-Induced Neurotoxicity in PC12 Cells via a Mitochondrial-Dependent Apoptosis Pathway

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 Aβ(25–35)-induced toxicity, as well as of its potential mechanisms of action in PC12 cells. Exposure of these cells to the Aβ(25–35) protein significantly increased cell viability loss and apoptosis. However, the effects induced by Aβ(25–35) were markedly reversed in the present of biochanin A. Pretreatment with biochanin A attenuated the cytotoxic effect of the Aβ(25–35) 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 Aβ(25–35) and that this drug attenuated Aβ(25–35)-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.