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