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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)91
JournalFrontiers in Pharmacology
Volume10
DOIs
Publication statusPublished - 2019

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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

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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.

In: Frontiers in Pharmacology, Vol. 10, 2019, p. 91.

Research output: Contribution to journalArticle

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. In: Frontiers in Pharmacology. 2019 ; Vol. 10. pp. 91.
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