Inducible nitric oxide synthase and cyclooxygenase-2 participate in anti-inflammatory and analgesic effects of the natural marine compound lemnalol from Formosan soft coral Lemnalia cervicorni

Eur J Pharmacol. 2008 Jan 14;578(2-3):323-31. doi: 10.1016/j.ejphar.2007.08.048. Epub 2007 Sep 20.

Abstract

Lemnalol (8-isopropyl-5-methyl-4-methylene-decahydro-1,5-cyclo-naphthalen-3-ol) is a natural compound isolated from the marine soft coral Lemnalia cervicorni. In the present study, the anti-inflammatory and anti-nociceptive properties of lemnalol were investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and carrageenan-injected rats, respectively. Our results demonstrate that lemnalol significantly inhibited the expression of the pro-inflammatory proteins, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in LPS-stimulated RAW 264.7 cells. An in vivo inflammation model was induced by intraplantar injection of carrageenan into rat hind paws. An intramuscular injection of lemnalol (15 mg/kg) 10 min before carrageenan injection resulted in significant inhibition of carrageenan-induced rat paw edema and thermal hyperalgesia behavior. Western blot experiments revealed that the carrageenan-induced expression of iNOS and COX-2 in paw tissue was significantly down-regulated by lemnalol. Moreover, post-intrathecal injection of lemnalol produced a dose-dependent anti-nociceptive effect in carrageenan-injected rats (1 and 5 microg). The present results indicate that the marine-derived compound lemnalol had anti-inflammatory and analgesic effects in LPS-stimulated RAW 264.7 cells and carrageenan-injected rats, respectively. In addition, inhibition of elevated iNOS and COX-2 protein expression as well as neurophil infiltration of carrageenan-injected paws may be involved in the beneficial effects of lemnalol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / isolation & purification
  • Analgesics / pharmacology*
  • Animals
  • Anthozoa* / chemistry
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Carrageenan
  • Cell Line
  • Cyclooxygenase 2 / metabolism*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hot Temperature
  • Hyperalgesia / etiology
  • Hyperalgesia / pathology
  • Hyperalgesia / physiopathology
  • Hyperalgesia / prevention & control*
  • Immunohistochemistry
  • Inflammation / chemically induced
  • Inflammation / complications
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Inflammation / prevention & control*
  • Injections, Spinal
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Male
  • Mice
  • Neutrophil Infiltration / drug effects
  • Nitric Oxide Synthase Type II / metabolism*
  • Pain Measurement
  • Pain Threshold / drug effects
  • Rats
  • Rats, Wistar
  • Sesquiterpenes / administration & dosage
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Time Factors

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • Sesquiterpenes
  • lemnalol
  • Carrageenan
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2