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Inhibition of Human Neutrophil Elastase by Pentacyclic Triterpenes

文献类型：期刊论文

作者Feng, Li2; Liu, Xiaoyu1; Zhu, Weiliang3; Guo, Fujiang2; Wu, Yingchun2; Wang, Rui2; Chen, Kaixian2,3; Huang, Cheng2; Li, Yiming2
刊名PLOS ONE
出版日期2013-12-20
卷号8期号:12
ISSN号1932-6203
DOI10.1371/journal.pone.0082794
文献子类Article
英文摘要Scope: Inhibiting human neutrophil elastase (HNE) is a promising strategy for treating inflammatory lung diseases, such as H1N1 and SARS virus infections. The use of sivelestat, the only clinically registered synthesized HNE inhibitor, is largely limited by its risk of organ toxicity because it irreversibly inhibits HNE. Therefore, potent reversible HNE inhibitors are promising alternatives to sivelestat. Methods and Results: An in vitro HNE inhibition assay was employed to screen a series of triterpenes. Six pentacyclic triterpenes, but not tetracyclic triterpenes, significantly inhibited HNE. Of these pentacyclic triterpenes, ursolic acid exhibited the highest inhibitory potency (IC50 = 5.51 mu M). The HNE inhibitory activity of ursolic acid was further verified using a mouse model of acute smoke-induced lung inflammation. The results of nuclear magnetic resonance and HNE inhibition kinetic analysis showed that the pentacyclic triterpenes competitively and reversibly inhibited HNE. Molecular docking experiments indicated that the molecular scaffold, 28-COOH, and a double bond at an appropriate location in the pentacyclic triterpenes are important for their inhibitory activity. Conclusion: Our results provide insights into the effects of pentacyclic triterpenes on lung inflammatory actions through reversible inhibition of HNE activity.
WOS关键词ACUTE LUNG INJURY ; CIGARETTE-SMOKE ; MOLECULAR DOCKING ; CDDO-ME ; PROTEASE INHIBITOR ; ASTRAGALOSIDE-IV ; OXIDATIVE STRESS ; DOWN-REGULATION ; HUMAN-LEUKOCYTE ; URSOLIC ACID
资助项目National Science and Technology Major Project of China[2009ZX09311-003] ; Program for Professors of Special Appointment (Eastern Scholar) in Shanghai Institutions of Higher Learning[2012-90] ; "Xinlin'' scholars and outstanding team training plan of SHUTCM[00000000] ; National Natural Science Foundation of China[81173518]
WOS研究方向Science & Technology - Other Topics
语种英语
出版者PUBLIC LIBRARY SCIENCE
WOS记录号WOS:000328745100058
源URL[http://119.78.100.183/handle/2S10ELR8/277332]  
专题天然药物化学研究室
药物发现与设计中心
通讯作者Huang, Cheng
作者单位1.Second Mil Med Univ, Dept Biol Chem, Shanghai, Peoples R China;
2.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China
推荐引用方式
GB/T 7714		 Feng, Li,Liu, Xiaoyu,Zhu, Weiliang,et al. Inhibition of Human Neutrophil Elastase by Pentacyclic Triterpenes[J]. PLOS ONE,2013,8(12).
APA Feng, Li.,Liu, Xiaoyu.,Zhu, Weiliang.,Guo, Fujiang.,Wu, Yingchun.,...&Li, Yiming.(2013).Inhibition of Human Neutrophil Elastase by Pentacyclic Triterpenes.PLOS ONE,8(12).
MLA Feng, Li,et al."Inhibition of Human Neutrophil Elastase by Pentacyclic Triterpenes".PLOS ONE 8.12(2013).

入库方式： OAI收割

来源：上海药物研究所

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