title: Mitragynine inhibits the COX-2 mRNA expression and prostaglandin E₂ production induced by lipopolysaccharide in RAW264.7 macrophage cells.
abstract: BACKGROUND
  [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.
  
  
  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.
authors.affiliation: Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm), Ministry of Science, Technology and Innovation (MOSTI), Sains@USM Complex, 10, Persiaran Bukit Jambul, 11900 Bayan Lepas, Pulau Pinang, Malaysia.
authors.forename: Zulkhurnain
authors.initials: Z
authors.lastname: Utar
authors.forename: Mohamed Isa Abdul
authors.initials: MI
authors.lastname: Majid
authors.forename: Mohd Ilham
authors.initials: MI
authors.lastname: Adenan
authors.forename: Mohd Fadzly Amar
authors.initials: MF
authors.lastname: Jamil
authors.forename: Tan Mei
authors.initials: TM
authors.lastname: Lan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D032065:Mitragyna / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D046948:Secologanin Tryptamine Alkaloids / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D010936:Plant Extracts; D012333:RNA, Messenger; D046948:Secologanin Tryptamine Alkaloids; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C001801:mitragynine; D015232:Dinoprostone