Parkinson's disease (PD) is a movement disorder characterized by a progressive loss of nigrostriatal dopaminergic neurons. Microglia activation and neuroinflammation have been associated with the pathogenesis of PD. Indeed, cytokines have been proposed as candidates that mediate the apoptotic cell death of dopaminergic neurons seen in PD. In this study, we investigated the effect of two natural polyphenols, resveratrol and quercetin, on neuroinflammation. For glial cells, we observed that lipopolysaccharide (LPS)-induced mRNA levels of two proinflammatory genes, interleukin 1-alpha and tumor necrosis factor-alpha, are strongly decreased by treatments with resveratrol or quercetin. We also undertook microglial-neuronal coculture to examine the influence of resveratrol and quercetin on dopaminergic neuronal cell death evoked by LPS-activated microglia. Cytotoxicity assays were performed to evaluate the percentage of cell death, with apoptotic cells identified by both the TdT-mediated dUTP nick end labeling technique and the detection of cleaved caspase-3. We report that treatment of N9 microglial cells with resveratrol or quercetin successfully reduced the inflammation-mediated apoptotic death of neuronal cells in our coculture system. Altogether our results demonstrate that resveratrol and quercetin diminished apoptotic neuronal cell death induced by microglial activation and suggest that these two phytoestrogens may be potent antiinflammatory compounds.
Alzheimer's disease (AD) is the most common form of dementia. Recently, a number of epidemiological studies have evidence that some dietary factors such as low antioxidants and vitamins intake could increase the risk of AD. In the opposite, diets rich in unsaturated fatty acids, in polyphenols, vitamins and antioxidants were identified as preventive factors. Several studies have reported that adherence to the Mediterranean diet (MeDi) was associated with a reduction in incident of dementia. The beneficial effect of MeDi may be the result of the association of some individual and non-identified food components and high consumption of olive oil. In this study we have investigated the protective effects of two components of olive oil, tyrosol (Tyr) and hydroxytyrosol (OH-Tyr), against Aβ-induced toxicity. In cultured neuroblastoma N2a cells, we found that Aβ(25-35) (100 µg/ml) treatment induced a decrease of glutathione (GSH) and the activation of the transcription factor NF-κB and cell death. Our results demonstrated that the number of cell death decreased when cells were co-treated with Aβ and Tyr or OH-Tyr. However, neither of these phenolic compounds was able to prevent the decrease of GSH induced by H(2)O(2) or Aβ. We found that the increase in the nuclear translocation of the NF-κB subunits after Aβ exposure was attenuated in the presence of Tyr or OH-Tyr. These results identified two individual food components of the MeDi as neuroprotective agent against Aβ and their potential involvement in the beneficial effect of the MeDi for the prevention of AD.
Oxidative stress and apoptosis are frequently cited to explain neuronal cell damage in various neurodegenerative disorders, such as Parkinson' s disease. Brassinosteroids (BRs) are phytosterols recognized to promote stress tolerance of vegetables via modulation of the antioxidative enzyme cascade. However, their antioxidative effects on mammalian neuronal cells have never been examined so far.
We analyzed the ability of 24-epibrassinolide (24-Epi), a natural BR, to protect neuronal PC12 cells from 1-methyl-4-phenylpyridinium- (MPP+-) induced oxidative stress and consequent apoptosis in dopaminergic neurons. Our results demonstrate that 24-Epi reduces the levels of intracellular reactive oxygen species and modulates superoxide dismutase, catalase, and glutathione peroxidase activities. Finally, we determined that the antioxidative properties of 24-Epi lead to the inhibition of MPP+-induced apoptosis by reducing DNA fragmentation as well as the Bax/Bcl-2 protein ratio and cleaved caspase-3. This is the first time that the potent antioxidant and neuroprotective role of 24-Epi has been shown in a mammalian neuronal cell line.
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