Frontiers in Pharmacology (Feb 2019)

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,
  • Chunmao Lin,
  • Vincent Hungshu Chang

DOI
https://doi.org/10.3389/fphar.2019.00091
Journal volume & issue
Vol. 10

Abstract

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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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