Abstract
Menispermum dauricum rhizome has been widely used in China to treat various cardiovascular and thrombosis disorders. Some studies have reported that the phenolic alkaloids of Menispermum dauricum rhizome (PAM) have protective effects against brain ischemia injury, but the mechanism of this action remains to be clarified. In the present study, we investigated the possible mechanisms of action of PAM on experimental brain ischemia injury. Oxygen and glucose deprivation (OGD) in rat primary cortical cultures and middle cerebral artery occlusion in rats were used to mimic ischemia-reperfusion injury, respectively. The results suggested that PAM protected rat primary cortical cultures against OGD-reoxygenation induced cytotoxicity. PAM decreased extracellular glutamate content and markedly prevented the effects induced by OGD on protein level of GLT-1 and EAAC1 glutamate transporters. In addition, it reduced intracellular ROS generation. In vivo, PAM significantly reduced cerebral infarct area and ameliorated neurological functional deficits at different time points. Our findings revealed that the possible mechanism of action of PAM protected against brain ischemia injury involves regulation of GLT-1, EAAC1 and ROS generation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / isolation & purification
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Alkaloids / pharmacology*
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Alkaloids / therapeutic use
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Animals
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Brain Ischemia / drug therapy*
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Brain Ischemia / metabolism
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Brain Ischemia / pathology
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Cell Hypoxia
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Cell Survival / drug effects
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Cells, Cultured
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Excitatory Amino Acid Transporter 2 / genetics
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Excitatory Amino Acid Transporter 2 / metabolism*
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Excitatory Amino Acid Transporter 3 / genetics
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Excitatory Amino Acid Transporter 3 / metabolism*
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Extracellular Fluid / chemistry
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Extracellular Fluid / metabolism
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Gene Expression / drug effects
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Glutamic Acid / chemistry
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Glutamic Acid / metabolism
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Lactate Dehydrogenases / metabolism
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Male
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Menispermum / chemistry*
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Neurons / drug effects
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Neurons / enzymology
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Neurons / physiology
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Neuroprotective Agents / isolation & purification
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Neuroprotective Agents / pharmacology*
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Neuroprotective Agents / therapeutic use
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Phenols / isolation & purification
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Phenols / pharmacology*
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Phenols / therapeutic use
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Plant Extracts / isolation & purification
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Plant Extracts / pharmacology
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Plant Extracts / therapeutic use
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Rats
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Rats, Sprague-Dawley
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Reactive Oxygen Species / metabolism*
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Reperfusion Injury / metabolism
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Reperfusion Injury / pathology
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Reperfusion Injury / prevention & control*
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Rhizome / chemistry
Substances
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Alkaloids
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Excitatory Amino Acid Transporter 2
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Excitatory Amino Acid Transporter 3
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Neuroprotective Agents
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Phenols
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Plant Extracts
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Reactive Oxygen Species
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Slc1a1 protein, rat
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Glutamic Acid
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Lactate Dehydrogenases