Neuroprotection by two polyphenols following excitotoxicity and experimental ischemia.
Brain ischemia induces neuronal loss which is caused in part by excitotoxicity and free radical formation. Here, we report that mangiferin and morin, two antioxidant polyphenols, are neuroprotective in both in vitro and in vivo models of ischemia. Cell death caused by glutamate in neuronal cultures was decreased in the presence of submicromolar concentrations of mangiferin or morin which in turn attenuated receptor-mediated calcium influx, oxidative stress as well as apoptosis. In addition, both antioxidants diminished the generation of free radicals and neuronal loss in the hippocampal CA1 region due to transient forebrain ischemia in rats when administered after the insult. Importantly, neuroprotection by these antioxidants was functionally relevant since treated-ischemic rats performed significantly better in three hippocampal-dependent behavioral tests. Together, these results indicate that mangiferin and morin have potent neuroprotectant activity which may be of therapeutic value for the treatment of acute neuronal damage and disability.
Gottlieb
Miroslav
M
Departamento de Neurociencias, Universidad del País Vasco, Leioa, Vizcaya, Spain.
Leal-Campanario
Rocío
R
Campos-Esparza
María Rosario
MR
Sánchez-Gómez
María Victoria
MV
Alberdi
Elena
E
Arranz
Amaia
A
Delgado-García
José María
JM
Gruart
Agnès
A
Matute
Carlos
C
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D003214:Conditioning, Classical / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005508:Food Deprivation; D007511:Ischemia / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D018696:Neuroprotective Agents; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D002118:Calcium