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. We measured serum cholesterol levels, brain N-methyl-D-aspartate receptor (NMDAR1) mRNA and protein expression and liver sterol 27-hydroxylase (Cyp27a1) mRNA expression, as well as a Morris water maze performance. The results showed that, compared to mice consuming the HFE diet alone, those also consuming phytosterols (the HFE + PS diet) significantly decreased mean serum low-density lipoprotein cholesterol levels and altered brain NMDAR1 mRNA and protein expression and liver Cyp27a1 mRNA expression. The Morris water maze experiments indicated that dietary phytosterol supplementation slightly decreased the escape latency (p = 0.07). Collectively, these observations suggest that consumption of phytosterols from early in life may help alleviate the detrimental effects of HFE diets in mice.

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

Soybean isoflavone (SIF) has been demonstrated to have neuroprotective effects induced by ß-amyloid peptides (Aß) 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 Aß1-42-treated group, a SIF + Aß1-42 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). The protein expression of OGG1, Bcl-xl, Bad, beta subunit of ATP synthase (ATPB) and pyruvate dehydrogenase (PDH) in brain was also measured. The results showed that the level of 8-OHdG in both SIF groups was significantly decreased compared to the Aß1-42-treated group (p < 0.05), while the mRNA and protein expression of OGG1 in the SIF + Aß1-42 groups were up-regulated compared with the Aß1-42-treated groups (p < 0.05). The expression of Bcl-xl was up-regulated in the SIF-treated group compared with the Aß1-42-treated groups (p < 0.05), while the expression of Bad was down-regulated in the two SIF-treated groups (p < 0.05). Aß1-42 significantly down-regulated the expression of ATPase and PDH proteins compared with the control group (p < 0.05). SIF reversed the down-regulation effects on the mitochondrial energy metabolic enzymes induced by Aß1-42 (p < 0.05) in the rats. These results suggest that SIF alleviate the oxidative stress in neurons and mitochondria of rat brains mediated by Aß1-42, and these protective effects might be associated with the regulation of OGG1, Bad, Bcl-xl, ATPB and PDH.

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

ß-amyloid peptides (Aß) 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 ß-amyloid peptides. In this study, we were investigating whether genistein could antagonize oxidative damage induced by ß-amyloid peptide 25-35 (Aß25-35) in bEND.3 cells, and also identifying the potential neuroprotective targets of genistein. Vitamin E was used as the positive control. The bEND.3 cells were pre-incubated with/out genistein or vitamin E for 2 h followed by the incubation with 25 µM A 25-35 for another 24 h. The reactive oxygen species (ROS), nitrotyrosine, cell redox state, mRNA or protein expressions of the factors on Nrf2 signaling pathway were measured after Aß25-35 treatment. The results showed that genistein alleviated the increase of ROS and nitrotyrosine production induced by Aß25-35, and maintained bEND.3 cell redox state by increasing GSH level and GSH/GSSG. Genistein could reverse the down-regulation of total protein and mRNA expression of NF-E2-related factor 2 (Nrf2), nuclear Nrf2, γ-glutamylcysteine synthetase (γ-GCS), phosphatidylinositol 3-kinase (PI3K) induced by Aß25-35; while PI3K inhibitor LY294002 could attenuate the activation effects of genistein on Nrf2, especially for the promotion of nuclear translocation. These results suggested that genistein could protect cerebrovascular endothelial cells from Aß25-35-induced oxidative damage. The potential mechanisms might be associated with the activation of Nrf2 signaling pathway by modulating PI3K activity.

Neuroprotection of soyabean isoflavone co-administration with folic acid against beta-amyloid 1-40-induced neurotoxicity in rats.

Soya isoflavones (SIF) and folic acid (FA) both confer the biological properties of antioxidation; however, the mechanism of their antioxidant effect on nervous system development is unclear. Our purpose is to investigate the neuroprotective effects of SIF, FA or co-administration of SIF with FA against beta-amyloid 1-40 (Abeta1-40)-induced learning and memory impairment in rats. In the present study, the learning and memory ability of rats and the amount of amyloid-positive neurons in the cerebral cortex and hippocampal CA1 area were measured. The levels of total antioxidant capacity (T-AOC), glutathione (GSH) and glutathione peroxidase (GSH-Px) in serum and brain tissue were also measured. The results showed that intracerebroventricular administration of Abeta1-40 resulted in a dramatic prolongation of the escape latency; however, in the SIF, FA and SIF+FA treatment groups, the functional deficits of learning and memory were significantly improved. Moreover, after Abeta1-40 injection, the levels of T-AOC and GSH were profoundly decreased, suggesting a decline of antioxidant activity in the rats. However, intragastric pre-treatment with SIF, or FA, or SIF+FA resulted in a significant increase of antioxidative activity. SIF, or FA, or SIF+FA treatments also reversed the Abeta1-40-induced increase in the amount of amyloid-positive neurons. These results suggest that: (1) learning or memory impairment in experimental rats was caused by Abeta1-40, which is probably attributed to Abeta-induced oxidative damage and deposition of beta-amyloid peptides in the brain; (2) pre-administration of SIF and/or FA may prevent the pathological alterations caused by Abeta1-40 treatment and the neuroprotective effects of SIF and/or FA are indicated.