Fluorine-Modified Rutaecarpine Exerts Cyclooxygenase-2 Inhibition and Anti-inflammatory Effects in Lungs

Chiming Lee, Jiahnhaur Liao, Seuhwa Chen, Chiaohan Yen, Yuchieh Lee, Shihhao Huang, Shengtung Huang, Chun Mao Lin, Vincent Hungshu Chang

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

Inflammation is the first step that leads to inflammatory cell migration, cytokine release, and myofibroblast formation. Myofibroblasts can deposit excess amounts of extracellular matrix. Cyclooxygenase (COX) inhibitor exhibits strong anti-inflammatory response; however, this is usually achieved with undesirable side effects. In this study, we demonstrated the effects of the fluorine-modified rutaecarpine (RUT), fluoro-2-methoxyrutaecarpine (F-RUT), in inflammatory damage in the lungs. Based on the results, F-RUT retained anti-inflammatory activity both in vitro and in vivo in lungs. Compared to the parent compound, F-RUT showed better COX-2 suppression as a COX-2-selective inhibitor with lower cytotoxicity, and enhanced molecular reactivity and biological activity. F-RUT was also observed to reduce reactive oxygen species (ROS) generation and inflammatory infiltrating neutrophils in lipopolysaccharide (LPS)-stimulated zebrafish and ovalbumin (OVA)/alum-challenged KLF-10-knockout mouse lungs, respectively. Furthermore, F-RUT ameliorated the respiratory function in OVA/alum-challenged BALB/c mice by maintaining the thickness of the blood-air barrier in mouse lungs. Overall, these data suggest that F-RUT may function as an effective therapeutic agent for inflammation-induced lung dysfunction, and a better selection for pharmaceutical purposes than conventionally used anti-inflammatory agents.
原文英語
頁(從 - 到)91
期刊Frontiers in Pharmacology
10
DOIs
出版狀態已發佈 - 2019

指紋

Fluorine
Cyclooxygenase 2
Anti-Inflammatory Agents
Lung
Myofibroblasts
Blood-Air Barrier
Cyclooxygenase Inhibitors
Cyclooxygenase 2 Inhibitors
Zebrafish
Knockout Mice
Cell Movement
Extracellular Matrix
Lipopolysaccharides
Reactive Oxygen Species
Pneumonia
Neutrophils
Cytokines
Inflammation
rutecarpine
Pharmaceutical Preparations

引用此文

Fluorine-Modified Rutaecarpine Exerts Cyclooxygenase-2 Inhibition and Anti-inflammatory Effects in Lungs. / Lee, Chiming; Liao, Jiahnhaur; Chen, Seuhwa; Yen, Chiaohan; Lee, Yuchieh; Huang, Shihhao; Huang, Shengtung; Lin, Chun Mao; Chang, Vincent Hungshu.

於: Frontiers in Pharmacology, 卷 10, 2019, p. 91.

研究成果: 雜誌貢獻文章

Lee, Chiming ; Liao, Jiahnhaur ; Chen, Seuhwa ; Yen, Chiaohan ; Lee, Yuchieh ; Huang, Shihhao ; Huang, Shengtung ; Lin, Chun Mao ; Chang, Vincent Hungshu. / Fluorine-Modified Rutaecarpine Exerts Cyclooxygenase-2 Inhibition and Anti-inflammatory Effects in Lungs. 於: Frontiers in Pharmacology. 2019 ; 卷 10. 頁 91.
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abstract = "Inflammation is the first step that leads to inflammatory cell migration, cytokine release, and myofibroblast formation. Myofibroblasts can deposit excess amounts of extracellular matrix. Cyclooxygenase (COX) inhibitor exhibits strong anti-inflammatory response; however, this is usually achieved with undesirable side effects. In this study, we demonstrated the effects of the fluorine-modified rutaecarpine (RUT), fluoro-2-methoxyrutaecarpine (F-RUT), in inflammatory damage in the lungs. Based on the results, F-RUT retained anti-inflammatory activity both in vitro and in vivo in lungs. Compared to the parent compound, F-RUT showed better COX-2 suppression as a COX-2-selective inhibitor with lower cytotoxicity, and enhanced molecular reactivity and biological activity. F-RUT was also observed to reduce reactive oxygen species (ROS) generation and inflammatory infiltrating neutrophils in lipopolysaccharide (LPS)-stimulated zebrafish and ovalbumin (OVA)/alum-challenged KLF-10-knockout mouse lungs, respectively. Furthermore, F-RUT ameliorated the respiratory function in OVA/alum-challenged BALB/c mice by maintaining the thickness of the blood-air barrier in mouse lungs. Overall, these data suggest that F-RUT may function as an effective therapeutic agent for inflammation-induced lung dysfunction, and a better selection for pharmaceutical purposes than conventionally used anti-inflammatory agents.",
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