Keap1 as Target of Genistein on Nrf2 Signaling Pathway Antagonizing Aβ induced Oxidative Damage of Cerebrovascular Endothelial Cells.

Background: β-amyloid peptides (Aβ) induced oxidative damage contributes to the pathogenesis of neurodegenerative diseases, and the cerebrovascular system is more vulnerable to oxidative stress. Our earlier study showed a clue that Genistein (Gen) might activate the Nf-E2 related factor 2 (Nrf2) pathway to protect cerebrovascular cells from oxidative damage induced by Aβ, but the specific mechanisms and regulation targets are unclear.

Objective: In this study, the anti-oxidative effects and the possible targets of Gen on regulating the Nrf2 pathway in bEnd.

Neurocalcin-delta: a potential memory-related factor in hippocampus of obese rats induced by high-fat diet.

Introduction: Aberrant protein expression within the hippocampus has recently been implicated in the pathogenesis of obesity-induced memory impairment.

Objectives: The objective of the current study was to search for specific memory-related factors in the hippocampus in obese rats.

Methods: Sprague-Dawley (SD) rats were fed either a high-fat (HF) diet or normal-fat (NF) diet for 10 weeks to obtain the control (CON), diet-induced obese rats (DIO) and diet-resistant (DR) rats.

Genistein Inhibits Aβ25-35-Induced Synaptic Toxicity and Regulates CaMKII/CREB Pathway in SH-SY5Y Cells.

Genistein (Gen), as a functional food in human diet, has shown many beneficial effects on neurodegenerative diseases such as Alzheimer's disease (AD). But the neuroprotective mechanism of Gen is not clear. Because synaptic failure is considered as the earliest phase in the pathogenesis of AD, we try to validate our hypothesis that synapse may be one target of Gen on protecting neurons.

Global DNA methylation was changed by a maternal high-lipid, high-energy diet during gestation and lactation in male adult mice liver.

An epigenetic mechanism has been suggested to explain the effects of the maternal diet on the development of disease in offspring. The present study aimed to observe the effects of a maternal high-lipid, high-energy (HLE) diet on the DNA methylation pattern of male offspring in mice. Female C57BL/6J mice were fed an HLE diet during gestation and lactation.

The oxysterol 27-hydroxycholesterol increases oxidative stress and regulate Nrf2 signaling pathway in astrocyte cells.

The disturbance in cholesterol metabolism has been considered as a cause of alzheimer's disease (AD), which dues to the oxidative damage and cell apoptosis in the brain. We aimed to investigate the toxicity and mechanism of AD-like pathology caused by cholesterol oxidation metabolite 27-hydroxycholesterol (27-OHC) in astrocyte cells. C6 cells were treated with 0, 5, 10, 20 µM 27-OHC for 24 h (h).

The effect of soybean isoflavone on the dysregulation of NMDA receptor signaling pathway induced by β-amyloid peptides 1-42 in rats.

Synaptic damage is the key factor of cognitive impairment. The purpose of this study was to understand the effect of soybean isoflavone (SIF) on synaptic damage induced by β-amyloid peptide 1-42 (Aβ1-42) in rats. Adult male Wistar rats were randomly divided into control, Aβ1-42, SIF, and SIF + Aβ1-42 (SIF pretreatment) groups according to body weight.

Soy isoflavone antagonizes the oxidative cerebrovascular injury induced by β-amyloid peptides 1-42 in rats.

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.

Adaptive responses by mouse fetus to a maternal HLE diet by downregulating SREBP1: a microarray- and bio-analytic-based study.

Maternal diet has long been recognized as a significant factor affecting offspring development and health, but the target genes affected by a maternal high-lipid diet are currently unknown. In this study, the gene expression profile of neonatal mouse liver was analyzed using gene chips to identify genes with significant up- or downregulated expression levels due to maternal high-fat diet during gestation. Real-time PCR and Western blotting were used to measure key genes selected using microarray.

Beta amyloid peptide (25-35) leading to inflammation through Toll-like receptors and the anti-inflammatory effect of genistein in BV-2 cells.

Genistein, the main soy isoflavone component, has received much attention for its potential multifunction. Here, we reported that in BV-2 cells, genistein significantly inhibited beta amyloid peptides 25-35 (Aβ25-35)-induced inflammatory response. The results indicated that Aβ25-35-stimulated BV-2 cells upregulated Toll-like receptors 2 and 4, Myd88, and IKK gene expression with the increasing expression of IL-6 and decreasing expression of TGF-β and IL-10.

Soybean isoflavone ameliorates β-amyloid 1-42-induced learning and memory deficit in rats by protecting synaptic structure and function.

This research aims to investigate whether soybean isoflavone (SIF) could alleviate the learning and memory deficit induced by β-amyloid peptides 1-42 (Aβ 1-42) by protecting the synapses of rats. Adult male Wistar rats were randomly allocated to the following groups: (1) control group; (2) Aβ 1-42 group; (3) SIF group; (4) SIF + Aβ 1-42 group (SIF pretreatment group) according to body weight. The 80 mg/kg/day of SIF was administered orally by gavage to the rats in SIF and SIF+Aβ 1-42 groups.

The effects of phytosterol supplementation on serum LDL-C levels and learning ability in mice fed a high-fat, high-energy diet from gestation onward.

A high-fat, high-energy (HFE) diet may be deleterious to the cardiovascular system and mental health. We previously reported that serum cholesterol levels and escape latency were significantly increased in mice by feeding them an HFE diet from gestation onward. In this study, we examined whether an HFE diet supplemented with phytosterols fed to pregnant C57BL/6j dams and their offspring would protect the HFE-diet-induced compromise of the offspring's learning capability.

Genistein alleviates the mitochondria-targeted DNA damage induced by β-amyloid peptides 25-35 in C6 glioma cells.

Reactive oxygen species (ROS) are mainly produced by mitochondria which can cause oxidative stress. It has been considered that mitochondrial damage induced by oxidative stress is related to Alzheimer's disease (AD). Besides, mitochondrial DNA (mtDNA) is more vulnerable to oxidative damage than other biomacromolecules, causing serious dysfunction to mitochondria.

Soy isoflavone alleviates Aβ1-42-induced impairment of learning and memory ability through the regulation of RAGE/LRP-1 in neuronal and vascular tissue.

The neuroprotective properties of soy isoflavone (SIF) have been demonstrated by our previous studies and others, but its potential mechanism is not clear. Because of the key role of neurovascular dysfunction in the pathogenesis of Alzheimer's disease (AD), we hypothesized neurovascular tissue might be one neuroprotective target of SIF. In the present study, learning and memory ability, β-amyloid (Aβ) expressions both in neurovascular tissue and plasma, the receptor for advanced glycation end products (RAGE), low-density lipoprotein receptor-related protein (LRP)-1, nuclear factor-κB p65 (NF-κB p65), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) expressions in neurovascular tissue were measured in Wistar rats following lateral cerebral ventricle administration of Aβ1-42 by miniosmotic pump with or without intragastric administration of SIF from 14 days before surgery to the end of experiment.

Soy isoflavone attenuates brain mitochondrial oxidative stress induced by β-amyloid peptides 1-42 injection in lateral cerebral ventricle.

The aim of this study is to investigate whether soy isoflavone (SIF) reduces oxidative stress and improves the antioxidant ability in mitochondria of rat brain damaged by injection of beta-amyloid peptides 1-42 (Aβ1-42). Forty Wistar rats were randomly divided into control, Aβ1-42, SIF + Aβ1-42, and SIF groups according to body weight. The rats in the SIF + Aβ1-42 group and SIF group were intragastrically administered SIF suspension in 0.

Antagonizing effects of soybean isoflavones on β-amyloid peptide-induced oxidative damage in neuron mitochondria of rats.

Soybean isoflavone (SIF) has been demonstrated to have neuroprotective effects induced by β-amyloid peptides (Aβ) through suppressing oxidative stress; however, the explicit mechanisms still remain uncovered. In the present study, 32 Wistar rats were randomly divided into four groups: an Aβ1-42-treated group, a SIF + Aβ1-42 group, a SIF-treated group and a control group. We measured the protein content of 8-hydroxydeoxyguanosine (8-OhdG) and mRNA expression of 8-oxoguanine DNA glycosylase (OGG1).

Flavonoids protect cerebrovascular endothelial cells through Nrf2 and PI3K from β-amyloid peptide-induced oxidative damage.

β-amyloid peptides (Aβ) induced cerebrovascular dysfunction has been recognized as a vital factor involved in the pathogenesis of neurodegeneration. Genistein, a flavonoid, has antioxidative properties to prevent neurodegeneration induced by β-amyloid peptides. In this study, we were investigating whether genistein could antagonize oxidative damage induced by β-amyloid peptide 25-35 (Aβ25-35) in bEND.

Genistein inhibits mitochondrial-targeted oxidative damage induced by beta-amyloid peptide 25-35 in PC12 cells.

The antioxidative properties of genistein (Gen) have been demonstrated by our previous studies and others, but its potential mechanism was not very clear. Because of the key role of mitochondria in oxidant production, we wondered if mitochondria were one of Gen's neuroprotective targets. In the present study we investigated whether Gen has protective effects on mitochondria damaged by Aβ25-35.