Mitragynine inhibits the COX-2 mRNA expression and prostaglandin E₂ production induced by lipopolysaccharide in RAW264.7 macrophage cells

J Ethnopharmacol. 2011 Jun 14;136(1):75-82. doi: 10.1016/j.jep.2011.04.011. Epub 2011 Apr 12.

Abstract

Ethnopharmacological relevance: [corrected] Mitragyna speciosa Korth (Rubiaceae) is one of the medicinal plants used traditionally to treat various types of diseases especially in Thailand and Malaysia. Its anti-inflammatory and analgesic properties in its crude form are well documented. In this study, the cellular mechanism involved in the anti-inflammatory effects of mitragynine, the major bioactive constituent, was investigated.

Materials and methods: The effects of mitragynine on the mRNA and protein expression of COX-1 and COX-2 and the production of prostaglandin E(2) (PGE(2)) were investigated in LPS-treated RAW264.7 macrophage cells. Quantitative RT-PCR was used to assess the mRNA expression of COX-1 and COX-2. Protein expression of COX-1 and COX-2 were assessed using Western blot analysis and the level of PGE(2) production was quantified using Parameter™ PGE(2) Assay (R&D Systems).

Results: Mitragynine produced a significant inhibition on the mRNA expression of COX-2 induced by LPS, in a dose dependent manner and this was followed by the reduction of PGE(2) production. On the other hand, the effects of mitragynine on COX-1 mRNA expression were found to be insignificant as compared to the control cells. However, the effect of mitragynine on COX-1 protein expression is dependent on concentration, with higher concentration of mitragynine producing a further reduction of COX-1 expression in LPS-treated cells.

Conclusions: These findings suggest that mitragynine suppressed PGE(2) production by inhibiting COX-2 expression in LPS-stimulated RAW264.7 macrophage cells. Mitragynine may be useful for the treatment of inflammatory conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cyclooxygenase 1 / genetics
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Dinoprostone / antagonists & inhibitors*
  • Dose-Response Relationship, Drug
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mitragyna / chemistry*
  • Plant Extracts / pharmacology*
  • RNA, Messenger / metabolism
  • Secologanin Tryptamine Alkaloids / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Cyclooxygenase 2 Inhibitors
  • Lipopolysaccharides
  • Plant Extracts
  • RNA, Messenger
  • Secologanin Tryptamine Alkaloids
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • mitragynine
  • Dinoprostone