A new class of COX-2 inhibitor, rutaecarpine from Evodia rutaecarpa

Inflamm Res. 1999 Dec;48(12):621-5. doi: 10.1007/s000110050512.


Objective and design: We investigated the effect of a new class of COX-2 inhibitor, rutaecarpine, on the production of PGD2 in bone marrow derived mast cells (BMMC) and PGE2 in COX-2 transfected HEK293 cells. Inflammation was induced by lambda-carrageenan in male Splague-Dawley (SD) rats.

Material: Rutaecarpine (8,13-Dihydroindolo[2',3':3,4]pyridol[2,1-b]quinazolin -5(7H)-one) was isolated from the fruits of Evodia rutaecarpa. BMMC were cultured with WEHI-3 conditioned medium. c-Kit ligand and IL-10 were obtained by their expression in baculovirus.

Methods: The generation of PGD2 and PGE2 were determined by their assay kit. COX-1 and COX-2 protein and mRNA expression was determined by BMMC in the presence of KL, LPS and IL-10.

Treatment: Rutaecarpine and indomethacin dissolved in 0.1% carboxymethyl cellulose was administered intraperitoneally and, 1 h later, lambda-carrageenan solution was injected to right hind paw of rats. Paw volumes were measured using plethysmometer 5 h after lambda-carrageenan injection.

Results: Rutaecarpine inhibited COX-2 and COX-1 dependent phases of PGD2 generation in BMMC in a concentration-dependent manner with an IC50 of 0.28 microM and 8.7 microM, respectively. It inhibited COX-2-dependent conversion of exogenous arachidonic acid to PGE2 in a dose-dependent manner by the COX-2-transfected HEK293 cells. However, rutaecarpine inhibited neither PLA2 and COX-1 activity nor COX-2 protein and mRNA expression up to the concentration of 30 microM in BMMC, indicating that rutaecarpine directly inhibited COX-2 activity. Furthermore, rutaecarpine showed in vivo anti-inflammatory activity on rat lambda-carrageenan induced paw edema by intraperitoneal administration.

Conclusion: Anti-inflammatory activity of Evodia rutaecarpa could be attributed at least in part by inhibition of COS-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Cell Line
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / isolation & purification
  • Cyclooxygenase Inhibitors / pharmacology*
  • Electrophoresis, Polyacrylamide Gel
  • Fruit / chemistry
  • Humans
  • Immunoblotting
  • Indole Alkaloids
  • Inflammation / chemically induced
  • Inflammation / prevention & control
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Plants, Medicinal / chemistry*
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Quinazolines
  • Rats
  • Rats, Sprague-Dawley
  • Transfection


  • Alkaloids
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Indole Alkaloids
  • Isoenzymes
  • Membrane Proteins
  • Plant Extracts
  • Quinazolines
  • rutecarpine
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, mouse
  • Ptgs1 protein, rat