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Phenolic Alkaloids from Menispermum dauricum Rhizome Protect against Brain Ischemia Injury via Regulation of GLT-1, EAAC1 and ROS Generation

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Author(s): Bo Zhao | Yang Chen | Xi Sun | Mei Zhou | Jie Ding | Jin-Jin Zhan | Lian-Jun Guo

Journal: Molecules
ISSN 1420-3049

Volume: 17;
Issue: 3;
Start page: 2725;
Date: 2012;
Original page

Keywords: Menispermum dauricum | phenolic alkaloids | brain ischemia-reperfusion | glutamate transporter | reactive oxygen species

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.
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