Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction
文献类型：期刊论文
| 作者 | Gao, Yuanxue2; Xu, Xiaojun2; Chang, Sai2; Wang, Yunjie2; Xu, Yazhou2; Ran, Siqi2; Huang, Zhangjian3; Li, Ping2; Li, Jia1 ; Zhang, Luyong2
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| 刊名 | TOXICOLOGY AND APPLIED PHARMACOLOGY
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| 出版日期 | 2015-12-01 |
| 卷号 | 289期号:2页码:142-154 |
| 关键词 | Totarol HO-1 Akt Neuroprotection Stroke |
| ISSN号 | 0041-008X |
| DOI | 10.1016/j.taap.2015.10.001 |
| 文献子类 | Article |
| 英文摘要 | The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3 beta phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague-Dawley rats, produced by occlusion of the middle cerebral artery for 2 h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD.These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress. (C) 2015 Elsevier Inc. All rights reserved. |
| WOS关键词 | GLUTAMATE-INDUCED NEUROTOXICITY ; CEREBRAL-ARTERY OCCLUSION ; RAT CEREBELLAR NEURONS ; KAPPA-B EXPRESSION ; UP-REGULATED PAKT ; OXIDATIVE STRESS ; HEME OXYGENASE ; MOLECULAR-MECHANISMS ; NUTRIENT DEPRIVATION ; NRF2-KEAP1 PATHWAY |
| 资助项目 | National Natural Science Foundation of China[21402241] ; Natural Science Foundation of Jiangsu Province, China[BK20130653] ; Program for Jiangsu Province "Shuang Chuang" Team[00000000] ; State Key Laboratory of Natural Medicines, China Pharmaceutical University[SKLNMKF201407] ; College Students Innovation Project for the R&D of Novel Drugs[J1030830] ; Fundamental Research Funds for the Central Universities[JKZD2013006] ; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry, China[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000365461900002 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276311]  |
| 专题 | 国家新药筛选中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物安全性评价中心 |
| 通讯作者 | Liao, Hong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.China Pharmaceut Univ, Jiangsu Key Lab Drug Screening, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China; 3.China Pharmaceut Univ, Jiangsu Key Lab Drug Discovery Metab Dis, Nanjing 210009, Jiangsu, Peoples R China; 4.Georgetown Univ, Med Ctr, Dept Physiol & Pharmacol, Washington, DC 20057 USA |
| 推荐引用方式 GB/T 7714 | Gao, Yuanxue,Xu, Xiaojun,Chang, Sai,et al. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2015,289(2):142-154. |
| APA | Gao, Yuanxue.,Xu, Xiaojun.,Chang, Sai.,Wang, Yunjie.,Xu, Yazhou.,...&Pang, Tao.(2015).Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction.TOXICOLOGY AND APPLIED PHARMACOLOGY,289(2),142-154. |
| MLA | Gao, Yuanxue,et al."Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction".TOXICOLOGY AND APPLIED PHARMACOLOGY 289.2(2015):142-154. |
入库方式： OAI收割
来源：上海药物研究所
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