title: Neuroprotective effects of oxymatrine against excitotoxicity partially through down-regulation of NR2B-containing NMDA receptors.
abstract: 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 24 h reperfusion, in vivo. In vitro cultured neurons challenged with N-methyl-D-aspartate (NMDA, 200 μM) 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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Yu-jiao
authors.initials: YJ
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Oudeng
authors.initials: O
authors.lastname: Gerile
authors.forename: Le
authors.initials: L
authors.lastname: Yang
authors.forename: Xu-bo
authors.initials: XB
authors.lastname: Li
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Guo
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.forename: Shui-bing
authors.initials: SB
authors.lastname: Liu
authors.forename: Ming-gao
authors.initials: MG
authors.lastname: Zhao
mesh_terms: D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011807:Quinolizines / Q000494:pharmacology / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015427:Reperfusion Injury / Q000517:prevention & control*; D029909:Sophora; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000093842:Matrines
chemical_list: D000470:Alkaloids; D002118:Calcium; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011807:Quinolizines; D016194:Receptors, N-Methyl-D-Aspartate; D051028:bcl-2-Associated X Protein; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; C037573:oxymatrine; D000093842:Matrines