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Protosappanin A inhibits oxidative and nitrative stress via interfering the interaction of transmembrane protein CD14 with Toll-like receptor-4 in lipopolysaccharide-induced BV-2 microglia
Zeng, Ke-Wu; Zhao, Ming-Bo; Ma, Zhi-Zhong; Jiang, Yong; Tu, Peng-Fei
关键词Oxidative Stress Nitrative Stress Protosappanin a Toll-like Receptor 4 Cd14
刊名INTERNATIONAL IMMUNOPHARMACOLOGY
2012-12-01
DOI10.1016/j.intimp.2012.09.004
14期:4页:558-569
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Immunology ; Pharmacology & Pharmacy
资助者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 ; 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
研究领域[WOS]Immunology ; Pharmacology & Pharmacy
关键词[WOS]NF-KAPPA-B ; ALZHEIMERS-DISEASE ; INNATE IMMUNITY ; CELL-DEATH ; IN-VITRO ; ACTIVATION ; INFLAMMATION ; BRAIN ; NEUROINFLAMMATION ; NEURODEGENERATION
英文摘要

Oxidative and nitrative stresses have been established to play a pivotal role in neuroinflammation. During inflammation-mediated neurodegenerative diseases, including Alzheimer′s disease and Parkinson′s disease, reactive oxygen species (ROS) and nitric oxide (NO) are produced by activated microglia, further inducing increas.ed neuronal injury in the brain. Protosappanin A (PTA) is a bioactive compound isolated from a traditional Chinese medicine, Caesalpinia sappan L. (Lignum Sappan), showing immunosuppressive effects. However, the molecular mechanisms responsible for the anti-oxidative and nitrative activity of PTA have not been elucidated, particularly in central nervous system. In this study, we found that PTA significantly inhibited ROS and NO production by suppression of NADPH oxidase and inducible nitric oxide synthase (iNOS) activity on lipopolysaccharide (LPS)-stimulated BV-2 microglia. Moreover. PTA modulated IKK/I kappa B/NF-kappa B inflammation signal pathway to inhibit the activity and expressions of NADPH oxidase and iNOS. A further study indicated that PTA didn′t inhibit LPS interaction with transmembrane protein CD14, which is a receptor for LPS binding. However, PTA interfered with the interaction of CD14 with Toll-like receptor (TLR4), an early cell event of IKK/I kappa B/NF-kappa B inflammation signal activation, resulting in a block on LPS translocation from CD14 to TLR4. Therefore, CD14/TLR4 interaction may be a potential drug target in neuroinflammation-related oxidative and nitrative stress. Taken together, these results suggest that PTA has anti-oxidative/nitrative activities on brain immune and neuroinflammation through regulation of CD14/TLR4-dependent IKK/I kappa B/NF-kappa B inflammation signal pathway. (c) 2012 Elsevier B.V. All rights reserved.

语种英语
所属项目编号2012ZX09301002-002-002 ; 30873072 ; 2012M510294
资助者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 ; 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
WOS记录号WOS:000313152900028
Citation statistics
Cited Times:17[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52935
Collection北京大学药学院
作者单位Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
Recommended Citation
GB/T 7714
Zeng, Ke-Wu,Zhao, Ming-Bo,Ma, Zhi-Zhong,et al. Protosappanin A inhibits oxidative and nitrative stress via interfering the interaction of transmembrane protein CD14 with Toll-like receptor-4 in lipopolysaccharide-induced BV-2 microglia[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2012,14(4):558-569.
APA Zeng, Ke-Wu,Zhao, Ming-Bo,Ma, Zhi-Zhong,Jiang, Yong,&Tu, Peng-Fei.(2012).Protosappanin A inhibits oxidative and nitrative stress via interfering the interaction of transmembrane protein CD14 with Toll-like receptor-4 in lipopolysaccharide-induced BV-2 microglia.INTERNATIONAL IMMUNOPHARMACOLOGY,14(4),558-569.
MLA Zeng, Ke-Wu,et al."Protosappanin A inhibits oxidative and nitrative stress via interfering the interaction of transmembrane protein CD14 with Toll-like receptor-4 in lipopolysaccharide-induced BV-2 microglia".INTERNATIONAL IMMUNOPHARMACOLOGY 14.4(2012):558-569.
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