Mangifera indica L. extract attenuates glutamate-induced neurotoxicity on rat cortical neurons.
Overstimulation of ionotropic glutamate receptors causes excitotoxic neuronal death contributing to neurodegenerative disorders. Massive influx of calcium in excitotoxicity provokes alterations in the membrane potential of mitochondria and increases the production of reactive oxygen species. Here we report that Mangifera indica L. extracts (MiE) prevent glutamate-induced excitotoxicity in primary cultured neurons of the rat cerebral cortex. To evaluate the effects of MiE on excitotoxicity, cells were stimulated with L-glutamic acid (50 microM; 10 min) alone or in the presence of MiE. Maximal protection (56%) was obtained with 2.5 microg/mL of MiE. In turn, we measured the effects of MiE on excitotoxic-induced oxidative stress and mitochondrial depolarization by fluorimetry using 5,6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and tetramethylrhodamine, respectively. Both parameters were effectively reduced by MiE at concentrations which showed neuroprotection. Mangiferin, an antioxidant polyphenol which is a major component of MiE, was also effective in preventing neuronal death, oxidative stress and mitochondrial depolarization. Maximal protection (64%) was obtained at 12.5 microg/mL of mangiferin which also attenuated oxidative stress and mitochondrial depolarization at the neuroprotective concentrations. Together, these results indicate that MiE is an efficient neuroprotector of excitotoxic neuronal death, indicates that mangiferin carries a substantial part of the antioxidant and neuroprotective activity of MiE, and that this natural extract has therapeutic potential to treat neurodegenerative disorders.
Lemus-Molina
Yeny
Y
Laboratorio de Farmacología, Departamento de Investigaciones Biomédicas, Centro de Química Farmacéutica, 200 y 21 Atabey, Playa, P.O. Box. 16042, Habana, Cuba.
Sánchez-Gómez
Maria Victoria
MV
Delgado-Hernández
René
R
Matute
Carlos
C
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018698:Glutamic Acid / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D031022:Mangifera; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
C501277:Mangifera indica extract; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D018698:Glutamic Acid