Genistein as a neuroprotective antioxidant attenuates redox imbalance induced by beta-amyloid peptides 25-35 in PC12 cells.
ABSTRACT Genistein (GEN), a principal component of soybean isoflavones, might possess the neuroprotective role through its antioxidant activity. However, the detailed mechanisms are unknown yet. The purpose of this study was to investigate whether GEN could alleviate oxidative damage induced by beta-amyloid peptides 25-35 (Abeta25-35) in PC12 cells.
The PC12 cells were pre-incubated with or without GEN for 2h following incubation with Abeta25-35 for another 24h. MTT was used to assess the cell viability. Hoechst 33342 staining was applied to determine the apoptotic cells. Confocal laser scanning microscopy was implemented to examine the reactive oxygen species (ROS) levels. Mitochondrial membrane potential (MMP) was measured by flow cytometry. Reduced and oxidized glutathione (GSH/GSSG) ratio was analyzed by using assay kits. Western blot analysis was performed to assess the proteins expression of NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and gamma-glutamylcysteine synthetase (gamma-GCS).
GEN attenuated the cytotoxicity and partially prevented apoptosis induced by Abeta25-35. GEN dramatically attenuated ROS levels induced by Abeta25-35 in PC12 cells. In addition, GEN significantly reversed the reduction of MMP caused by Abeta25-35 to maintain the normal levels of the cells. The GSH/GSSG ratio in GEN pretreated groups significantly increased compared to the groups without GEN pretreatment. GEN reversed Abeta25-35 induced down regulation of the protein expression of gamma-GCS, Nrf2 and HO-1.
GEN could alleviate the oxidative stress caused by Abeta25-35 treatment and maintain redox balance in PC12 cells, which might be associated with the regulation of Nrf2/HO-1 signal pathway.
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ABSTRACT: Covering: 2000 to 2013Oxidative stress is the central component of chronic diseases. The nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway is vital in the up-regulation of cytoprotective genes and enzymes in response to oxidative stress and treatment with certain dietary phytochemicals. Herein, we classify bioactive compounds derived from natural products that are Nrf2/ARE pathway activators and recapitulate the molecular mechanisms for inducing Nrf2 to provide favorable effects in experimental models of chronic diseases. Moreover, pharmacological inhibition of Nrf2 signalling has emerged as promising strategy against multi-drug resistance thereby improving the treatment efficacy. We have also enlisted natural product-derived inhibitors of Nrf2/ARE pathway.Natural Product Reports 11/2013; · 10.18 Impact Factor
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ABSTRACT: Numerous evidences have shown that the antioxidative properties of soy isoflavone (SIF) have beneficial effects on prophylaxis of neurodegeneration, however, the mechanism is still not fully illustrated. As cerebrovascular dysfunction could initiate a cascade of events leading to pathogenesis of Alzheimer's disease, we tried to investigate whether SIF could protect the cerebrovascular system due to antagonizing oxidative damage induced by Aβ1-42 in present study. In addition, NF-E2-related factor 2 (Nrf2) signaling pathways in the cerebrovascular tissue of Wistar rats were investigated to identify the potential cerebrovascular protective targets of SIF. Research results showed that SIF reduced the excessive production of nitrotyrosine in cerebrovascular tissue induced by Aβ1-42, and maintained redox homeostasis by increasing the level of GSH and GSH/GSSG. Moreover, SIF could alleviate the down-regulation of Nrf2, γ-glutamylcysteine synthetase, Heme oxygenase-1 expressions in cerebrovascular tissue induced by Aβ1-42 and suppress the increase of Kelch like ECH protein-1 (Keap1). These data suggested that SIF might reduce the cerebrovascular oxidative damage induced by Aβ1-42 through regulating the Nrf2 signaling pathway. The mechanisms of SIF modulating the potential target Nrf2 might be associated with Keap1 expression.Neurochemical Research 05/2014; · 2.13 Impact Factor
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ABSTRACT: Pathologically, Alzheimer's disease is a result of aggregation of amyloid peptides and protein tau in the brain forming neurofibrillary tangles which are highly toxic to neuronal circuits in the brain. Recent evidences report that apart from aging, estrogen deficiency is one of the risk factors predisposing to the development of Alzheimer's disease. Isofla-vones, also known as phytoestrogens, are metabolized by the body forming compounds that are known to interfere with neurotoxic pathways and through their anti-fibrillization effects they play a role in reducing apoptosis of neurons and glial cells and promote axonal regeneration. Experimental studies on transgenic models with Alzheimer's disease as well as various observational and clinical trials suggest that dietary interventions with Isoflavones may have a significant role in improving portions of memory, cognition and decreasing the risk of Alzheimer's disease.Pakistan Journal of Neurological Sciences. 05/2014; 9(April - June 2014):40-45.