Synthetic fluororutaecarpine inhibits inflammatory stimuli and activates endothelial transient receptor potential vanilloid-type 1

Chi-Ming Lee, Jiun An Gu, Tin Gan Rau, Chi Wang, Chiao Han Yen, Shih Hao Huang, Feng Yen Lin, Chun Mao Lin, Sheng Tung Huang

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5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number656
JournalMolecules
Volume22
Issue number4
DOIs
Publication statusPublished - Apr 1 2017

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Keywords

  • ENOS
  • Fluoro-rutaecarpine
  • Inflammation
  • INOS
  • TRPV-1

ASJC Scopus subject areas

  • Medicine(all)
  • Organic Chemistry

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