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

• Published in: Molecules (Basel, Switzerland) Vol. 21; no. 5; p. 548
• Main Authors: Tan, Ji Wei, Kim, Min Kyu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 25.04.2016; MDPI AG
• Subjects: Alzheimer’s disease; Amyloid beta-Peptides - toxicity; Animals; Apoptosis; beta-amyloid; biochanin A; Cell Survival - drug effects; Gene Expression Regulation - drug effects; Genistein - pharmacology; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; mitochondrial dysfunction; Neurons - drug effects; Neuroprotective Agents - pharmacology; PC12 Cells; Peptide Fragments - toxicity; Rats; Signal Transduction - drug effects; beta-amyloid; apoptosis; biochanin A; mitochondrial dysfunction; Alzheimer’s disease; PC12 cells
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules21050548

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.