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Molecules 2016, 21(8), 1093;

Neuroprotection by Combined Administration with Maslinic Acid, a Natural Product from Olea europaea, and MK-801 in the Cerebral Ischemia Model

Institute of Translational Medicine, Nanchang University, 1299 Xuefu Avenue, Nanchang 330001, China
Department of Physiology, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China
Department of Human Anatomy and Cell Science, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, MB R3E 0J9, Canada
Center for Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China
Authors to whom correspondence should be addressed.
Academic Editor: Peter Koulen
Received: 19 June 2016 / Revised: 15 August 2016 / Accepted: 17 August 2016 / Published: 19 August 2016
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Glutamate-mediated excitotoxicity is a major cause of ischemic brain damage. MK-801 confers neuroprotection by attenuating the activation of the N-methyl-d-aspartate (NMDA) receptor, but it failed in clinical use due to the short therapeutic window. Here we aim to investigate the effects of maslinic acid, a natural product from Olea europaea, on the therapeutic time window and dose range for the neuroprotection of MK-801. Rats were administered with maslinic acid intracerebroventricularly and cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) followed by reperfusion. MK-801 was administered at 1 h, 2 h, 3 h and 4 h after ischemia, respectively. The cerebral infarct volume was determined by 2,3,5-Triphenyltetrazolium chloride (TTC) staining, neuronal damage was assessed by Haematoxylin Eosin (H&E) staining, and the expression of glial glutamate transporters and glial fibrillary acidic protein (GFAP) was evaluated by immunohistochemistry and Western blot post-ischemia. Results showed that the presence of maslinic acid extended the therapeutic time window for MK-801 from 1 h to 3 h. Co-treatment of maslinic acid and MK-801 at a subthreshold dosage obviously induced neuroprotection after ischemia. The combination of these two compounds improved the outcome in ischemic rats. Moreover, maslinic acid treatment promoted the expression of GLT-1 and GFAP post-ischemia. These data suggest that the synergistic effect of maslinic acid on neurological protection might be associated with the improvement of glial function, especially with the increased expression of GLT-1. The combination therapy of maslinic acid and MK-801 may prove to be a potential strategy for treating acute ischemic stroke. View Full-Text
Keywords: cerebral ischemia; maslinic acid; MK-801; GLT-1 cerebral ischemia; maslinic acid; MK-801; GLT-1

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Qian, Y.; Tang, X.; Guan, T.; Li, Y.; Sun, H. Neuroprotection by Combined Administration with Maslinic Acid, a Natural Product from Olea europaea, and MK-801 in the Cerebral Ischemia Model. Molecules 2016, 21, 1093.

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