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Anti-neuroinflammatory efficacy of the aldose reductase inhibitor FMHM via phospholipase C/protein kinase C-dependent NF-kappa B and MAPK pathways
Zeng, Ke-Wu1; Li, Jun2; Dong, Xin1; Wang, Ying-Hong1; Ma, Zhi-Zhong1; Jiang, Yong1; Jin, Hong-Wei1; Tu, Peng-Fei1,2
关键词Aldose reductase Protein kinase C Nuclear factor-kappa B (NF-kappa B) Neuroinflammation Microglia
刊名TOXICOLOGY AND APPLIED PHARMACOLOGY
2013-11-15
DOI10.1016/j.taap.2013.08.028
273期:1页:159-171
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]Pharmacology & Pharmacy ; Toxicology
关键词[WOS]NERVE CONDUCTION-VELOCITY ; NEURODEGENERATIVE DISEASES ; PROTEIN-KINASE ; THERAPEUTIC AGENTS ; NITRIC-OXIDE ; INFLAMMATION ; MICROGLIA ; ACTIVATION ; RECEPTOR ; MACROPHAGES
英文摘要

Aldose reductase (AR) has a key role in several inflammatory diseases: diabetes, cancer and cardiovascular diseases. Therefore, AR inhibition seems to be a useful strategy for anti-inflammation therapy. In the central nervous system (CNS), microglial over-activation is considered to be a central event in neuroinflammation. However, the effects of AR inhibition in CNS inflammation and its underlying mechanism of action remain unknown. In the present study, we found that FMHM (a naturally derived AR inhibitor from the roots of Polygala tricornis Gagnep.) showed potent anti-neuroinflammatory effects in vivo and in vitro by inhibiting microglial activation and expression of inflammatory mediators. Mechanistic studies showed that FMHM suppressed the activity of AR-dependent phospholipase C/protein kinase C signaling, which further resulted in downstream inactivation of the I kappa B kinase/I kappa B/nuclear factor-kappa B (NF-kappa B) inflammatory pathway. Therefore, AR inhibition-dependent NF-kappa B inactivation negatively regulated the transcription and expression of various inflammatory genes. AR inhibition by FMHM exerted neuroprotective effects in lipopolysaccharide-induced neuron-microglia co-cultures. These findings suggested that AR is a potential target for neuroinflammation inhibition and that FMHM could be an effective agent for treating or preventing neuroinflammatory diseases. (C) 2013 Elsevier Inc. All rights reserved.

语种英语
WOS记录号WOS:000327290000017
项目编号2012ZX09301002-002-002 ; 81303253 ; 30873072 ; 2012M510294 ; 2013T60045
资助机构National Key Technology R &amp ; D Program "New Drug Innovation" of China ; Natural Science Foundation of China ; China Postdoctoral Science Foundation ; Postdoctoral Fellowship of Peking-Tsinghua Center for Life Sciences
引用统计
被引频次:21[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64661
专题北京大学药学院
北京大学基础医学院
北京大学药学院_天然药物与仿生药物国家重点实验室
北京大学药学院_天然药物学系
作者单位1.Peking Univ, Hlth Sci Ctr, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
2.Beijing Univ Chinese Med, Modern Res Ctr Tradit Chinese Med, Beijing 100029, Peoples R China
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GB/T 7714
Zeng, Ke-Wu,Li, Jun,Dong, Xin,et al. Anti-neuroinflammatory efficacy of the aldose reductase inhibitor FMHM via phospholipase C/protein kinase C-dependent NF-kappa B and MAPK pathways[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2013,273(1):159-171.
APA Zeng, Ke-Wu.,Li, Jun.,Dong, Xin.,Wang, Ying-Hong.,Ma, Zhi-Zhong.,...&Tu, Peng-Fei.(2013).Anti-neuroinflammatory efficacy of the aldose reductase inhibitor FMHM via phospholipase C/protein kinase C-dependent NF-kappa B and MAPK pathways.TOXICOLOGY AND APPLIED PHARMACOLOGY,273(1),159-171.
MLA Zeng, Ke-Wu,et al."Anti-neuroinflammatory efficacy of the aldose reductase inhibitor FMHM via phospholipase C/protein kinase C-dependent NF-kappa B and MAPK pathways".TOXICOLOGY AND APPLIED PHARMACOLOGY 273.1(2013):159-171.
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