Inhibition of human neutrophil elastase by pentacyclic triterpenes.

<h4>Scope</h4>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 toxic...

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Autores principales:	Li Feng, Xiaoyu Liu, Weiliang Zhu, Fujiang Guo, Yingchun Wu, Rui Wang, Kaixian Chen, Cheng Huang, Yiming Li
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5736b69e0d9444e785eebe67e0396048
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spelling	oai:doaj.org-article:5736b69e0d9444e785eebe67e03960482021-11-18T08:40:58ZInhibition of human neutrophil elastase by pentacyclic triterpenes.1932-620310.1371/journal.pone.0082794https://doaj.org/article/5736b69e0d9444e785eebe67e03960482013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24376583/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Scope</h4>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.<h4>Methods and results</h4>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 µM). 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.<h4>Conclusion</h4>Our results provide insights into the effects of pentacyclic triterpenes on lung inflammatory actions through reversible inhibition of HNE activity.Li FengXiaoyu LiuWeiliang ZhuFujiang GuoYingchun WuRui WangKaixian ChenCheng HuangYiming LiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e82794 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Li Feng Xiaoyu Liu Weiliang Zhu Fujiang Guo Yingchun Wu Rui Wang Kaixian Chen Cheng Huang Yiming Li Inhibition of human neutrophil elastase by pentacyclic triterpenes.
description	<h4>Scope</h4>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.<h4>Methods and results</h4>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 µM). 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.<h4>Conclusion</h4>Our results provide insights into the effects of pentacyclic triterpenes on lung inflammatory actions through reversible inhibition of HNE activity.
format	article
author	Li Feng Xiaoyu Liu Weiliang Zhu Fujiang Guo Yingchun Wu Rui Wang Kaixian Chen Cheng Huang Yiming Li
author_facet	Li Feng Xiaoyu Liu Weiliang Zhu Fujiang Guo Yingchun Wu Rui Wang Kaixian Chen Cheng Huang Yiming Li
author_sort	Li Feng
title	Inhibition of human neutrophil elastase by pentacyclic triterpenes.
title_short	Inhibition of human neutrophil elastase by pentacyclic triterpenes.
title_full	Inhibition of human neutrophil elastase by pentacyclic triterpenes.
title_fullStr	Inhibition of human neutrophil elastase by pentacyclic triterpenes.
title_full_unstemmed	Inhibition of human neutrophil elastase by pentacyclic triterpenes.
title_sort	inhibition of human neutrophil elastase by pentacyclic triterpenes.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/5736b69e0d9444e785eebe67e0396048
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Inhibition of human neutrophil elastase by pentacyclic triterpenes.

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