morin and mangiferin

Amyloid beta- (A

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Apoptosis; Calcium; Cell Death; Cell Survival; Cells, Cultured; Cytosol; Flavonoids; Immunohistochemistry; Membrane Potential, Mitochondrial; Mitochondria; Neurons; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Xanthones

Excessive activation of glutamate receptors, or excitotoxicity, contributes to acute and chronic neurological disorders including stroke. We previously showed that two natural polyphenol antioxidants, mangiferin and morin, are neuroprotective in a model of ischemic brain damage. In this study, we analyzed the molecular mechanisms underlying neuroprotection by mangiferin and morin in an in vitro model of excitotoxic neuronal death involving NMDA receptor overactivation. We observed that both polyphenols reduce the formation of reactive oxygen species, activate the enzymatic antioxidant system, and restore the mitochondrial membrane potential. Moreover, both antioxidants inhibit glutamate-induced activation of calpains, normalize the levels of phosphorylated Akt kinase and Erk1/2, as well as of cytosolic Bax, inhibit AIF release from mitochondria, and regulate the nuclear translocation of NF-kappaB. Each of these effects contributes to the substantial reduction of apoptotic neuronal death induced by glutamate. These results demonstrate that mangiferin and morin exhibit excellent antioxidant and antiapoptotic properties, supporting their clinical application as trial neuroprotectors in pathologies involving excitotoxic neuronal death.

Topics: Animals; Antioxidants; Apoptosis Regulatory Proteins; Calpain; Caspases; Cell Death; Cell Nucleus; Cerebral Cortex; Cytoprotection; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Glutamic Acid; Membrane Potential, Mitochondrial; Neurons; Neuroprotective Agents; Neurotoxins; NF-kappa B; Phenols; Polyphenols; Protein Transport; Proto-Oncogene Proteins c-akt; Rats; Reactive Oxygen Species; Xanthones

Oligodendrocytes are vulnerable to overactivation of both their AMPA receptors and their high- and low-affinity kainate receptors. Depending on the intensity of the insult and the type of receptor activated, excitotoxic oligodendrocyte death mediated by these receptors has different characteristics. One important consequence at a cellular level is the ensuing oxidative stress, related to Ca2+-dependent alterations in mitochondrial functioning. We observed that oxidative stress associated with selective AMPA receptor activation is much higher than that associated with the selective activation of high- and low-affinity kainate receptors. Moreover, excitotoxic insults generate more intense oxidative stress in oligodendrocytes than in cortical neurons, though similar alterations in [Ca2+]i and mitochondrial potential were observed in both cell types. Nanomolar concentrations of mangiferin and morin, two natural polyphenols with antioxidant properties, partially protect oligodendrocytes as well as cortical neurons from mild, but not intense, insults mediated by AMPA receptors. In addition to presenting oxygen radical scavenging activity, mangiferin and morin attenuate the intracellular Ca2+ overload subsequent to the activation of AMPA receptors, a mechanism that may contribute to their protective properties. The inclusion of these antioxidant agents in therapeutic strategies for the treatment of diseases in which oligodendrocyte as well as neuron loss occurs may prove to be beneficial.

Topics: Animals; Antioxidants; Calcium; Caspase 3; Caspases; Cell Survival; Cytosol; Flavonoids; Free Radical Scavengers; Mitochondria; Neurons; Neuroprotective Agents; Neurotoxins; Oligodendroglia; Optic Nerve; Oxidative Stress; Phenols; Polyphenols; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Receptors, AMPA; Receptors, Kainic Acid; Xanthones