Journal
PHYTOMEDICINE
Volume 20, Issue 3-4, Pages 343-350Publisher
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.phymed.2012.10.018
Keywords
Oxymatrine; Apoptosis; Neuron; N-methyl-D-aspartate; Middle cerebral artery occlusion
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Funding
- NSF of China [31070923, 2009ZX09103-111]
- Program for New Century Excellent Talents in University
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Oxymatrine (OMT) is a major bioactive component derived from Sophora flavescens Ait (kushen), which is widely used in Chinese medicine. Recent studies have shown that it has neuroprotective effects; however, its underlying mechanisms remain unclear. We focus on the mechanisms of pharmacologic action in OMT by detecting its pharmacological properties against focal cerebral ischemia in vivo and NMDA-induced neurotoxicity in vitro. OMT prevented cerebral ischemic injury in mice induced via a 2 h middle cerebral artery occlusion and a 24h reperfusion, in vivo. In-vitro cultured neurons challenged with N-methyl-D-aspartate (NMDA, 200 mu M) for 30 min showed significant decrease in the viability of neurons; however, OMT was able to protect neurons against induced neurotoxicity via NMDA exposure. Western blot analysis revealed that OMT decreased the expression of Bax and repaired the balance of pro- and anti-apoptotic proteins. Furthermore, OMT significantly reversed the up-regulation of NR2B and inhibited the calcium overload in the cultured neurons after challenging the NMDA. OMT showed partial protection in the cortical neurons via down-regulation of NR2B containing NMDA receptors and up-regulation of Bcl-2 family. Our results provide new insights into the development of natural therapeutic anti-oxidants against ischemia. (C) 2012 Elsevier GmbH. All rights reserved.
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