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

Abstract

Abstract: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][26][27][28][29][30][31][32][33][34][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.

Antiproliferative Activity of Combined Biochanin A and Ginsenoside Rh2 on MDA-MB-231 and MCF-7 Human Breast Cancer Cells

“…BA and Rh 2 both show no cytotoxicity at doses of 10–100 µM (data not shown). These data is supported by previous work performed by Tan and Kim reporting that 100 μM BA had no toxic effects in PC12 cells [ 18 ]. Furthermore, Quan’s studies have shown that Rh 2 at 80 µM dose exhibited no cytotoxic activity in the cells [ 19 ].…”

Therapeutic Potentials of Microalgae in the Treatment of Alzheimer’s Disease

“…Biochanin A is an isoflavone with estrogenic activity in humans and has been identified in C. vulgaris [ 155 ]. Biochanin A exhibits neuroprotective activity against Aβ-induced neurotoxicity in PC-12 cells [ 156 ]. Furthermore, some carotenoids also protect the neurons against β-amyloid-induced neurotoxicity.…”

The Identification of Biochanin A as a Potent and Selective β-Site App-Cleaving Enzyme 1 (Bace1) Inhibitor

“…Over the past few years, the research on the isoflavones has mostly been focused on genistein, and the limited number of studies have been performed on the role of biochanin A. Interestingly, in our ongoing research of exploring natural BACE1 inhibitor, biochanin A exhibited significant BACE1 suppressing property compared with the other isoflavones including genistein. Furthermore, previous studies regarding on biochanin A displayed marked neuroprotective properties [14,15,16,17]. Biochanin A attenuated Aβ 25–35 -induced PC12 cell injury and apoptosis via preventing mitochondrial dysfunction [14].…”

“…Furthermore, previous studies regarding on biochanin A displayed marked neuroprotective properties [14,15,16,17]. Biochanin A attenuated Aβ 25–35 -induced PC12 cell injury and apoptosis via preventing mitochondrial dysfunction [14]. The compound protected dopaminergic neurons against LPS-induced damage through inhibition of microglia activation and production of proinflammatory factors [15].…”