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Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1

The natural product, rutaecarpine (RUT), is the main effective component of Evodia rutaecarpa which is a widely used traditional Chinese medicine. It has vasodilation, anticoagulation, and anti-inflammatory activities. However, further therapeutic applications are limited by its cytotoxicity. Thus,...

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Autores principales: Lee, Chi-Ming, Gu, Jiun-An, Rau, Tin-Gan, Wang, Chi, Yen, Chiao-Han, Huang, Shih-Hao, Lin, Feng-Yen, Lin, Chun-Mao, Huang, Sheng-Tung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153741/
https://www.ncbi.nlm.nih.gov/pubmed/28422079
http://dx.doi.org/10.3390/molecules22040656
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author Lee, Chi-Ming
Gu, Jiun-An
Rau, Tin-Gan
Wang, Chi
Yen, Chiao-Han
Huang, Shih-Hao
Lin, Feng-Yen
Lin, Chun-Mao
Huang, Sheng-Tung
author_facet Lee, Chi-Ming
Gu, Jiun-An
Rau, Tin-Gan
Wang, Chi
Yen, Chiao-Han
Huang, Shih-Hao
Lin, Feng-Yen
Lin, Chun-Mao
Huang, Sheng-Tung
author_sort Lee, Chi-Ming
collection PubMed
description The natural product, rutaecarpine (RUT), is the main effective component of Evodia rutaecarpa which is a widely used traditional Chinese medicine. It has vasodilation, anticoagulation, and anti-inflammatory activities. However, further therapeutic applications are limited by its cytotoxicity. Thus, a derivative of RUT, 10-fluoro-2-methoxyrutaecarpine (F-RUT), was designed and synthesized that showed no cytotoxicity toward RAW264.7 macrophages at 20 μM. In an anti-inflammation experiment, it inhibited the production of nitric oxide (NO) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages; cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) induced by LPS were also downregulated. After 24 h of treatment, F-RUT significantly inhibited cell migration and invasion of ovarian A2780 cells. Furthermore, F-RUT promoted expressions of transient receptor potential vanilloid type 1 (TRPV1) and endothelial (e)NOS in human aortic endothelial cells, and predominantly reduced the inflammation in ovalbumin/alum-challenged mice. These results suggest that the novel synthetic F-RUT exerts activities against inflammation and vasodilation, while displaying less toxicity than its lead compound.
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spelling pubmed-61537412018-11-13 Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1 Lee, Chi-Ming Gu, Jiun-An Rau, Tin-Gan Wang, Chi Yen, Chiao-Han Huang, Shih-Hao Lin, Feng-Yen Lin, Chun-Mao Huang, Sheng-Tung Molecules Article The natural product, rutaecarpine (RUT), is the main effective component of Evodia rutaecarpa which is a widely used traditional Chinese medicine. It has vasodilation, anticoagulation, and anti-inflammatory activities. However, further therapeutic applications are limited by its cytotoxicity. Thus, a derivative of RUT, 10-fluoro-2-methoxyrutaecarpine (F-RUT), was designed and synthesized that showed no cytotoxicity toward RAW264.7 macrophages at 20 μM. In an anti-inflammation experiment, it inhibited the production of nitric oxide (NO) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages; cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) induced by LPS were also downregulated. After 24 h of treatment, F-RUT significantly inhibited cell migration and invasion of ovarian A2780 cells. Furthermore, F-RUT promoted expressions of transient receptor potential vanilloid type 1 (TRPV1) and endothelial (e)NOS in human aortic endothelial cells, and predominantly reduced the inflammation in ovalbumin/alum-challenged mice. These results suggest that the novel synthetic F-RUT exerts activities against inflammation and vasodilation, while displaying less toxicity than its lead compound. MDPI 2017-04-19 /pmc/articles/PMC6153741/ /pubmed/28422079 http://dx.doi.org/10.3390/molecules22040656 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Chi-Ming
Gu, Jiun-An
Rau, Tin-Gan
Wang, Chi
Yen, Chiao-Han
Huang, Shih-Hao
Lin, Feng-Yen
Lin, Chun-Mao
Huang, Sheng-Tung
Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1
title Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1
title_full Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1
title_fullStr Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1
title_full_unstemmed Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1
title_short Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1
title_sort synthetic fluororutaecarpine inhibits inflammatory stimuli and activates endothelial transient receptor potential vanilloid-type 1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153741/
https://www.ncbi.nlm.nih.gov/pubmed/28422079
http://dx.doi.org/10.3390/molecules22040656
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