The analgesic and anti-inflammatory effect of new oleanolic acid acyloxyimino derivative

Eur J Pharm Sci. 2012 Oct 9;47(3):549-55. doi: 10.1016/j.ejps.2012.07.017. Epub 2012 Jul 31.

Abstract

The new derivative of well-known triterpene, oleanolic acid: methyl 3-octanoyloxyiminoolean-12-en-28-oate 5, was synthesized by the action of caprylic acid on methyl oleanolate 3-oxime in the presence of dicyclohexylcarbodiimide in dioxane. The molecular structure of the obtained product 5 was confirmed by spectral methods. The acute toxicity, locomotor activity, and the dose-dependent analgesic activity were studied. In addition, the effect of compound 5 on morphine-induced analgesic activity, the dose-dependent anti-inflammatory activity and the effect of the compound on diclofenac anti-inflammatory activity study were performed. The results proved a low toxicity (LD₅₀ > 2 g/kg) of the tested product 5, which affected neither vertical nor horizontal locomotor activity in the given range of doses. The triterpene 5 also produced centrally mediated (morphine-like) analgesic action; however, only in the highest dose. The synergistic analgesic activity of 5 and morphine in the doses of 30.0 and 300.0mg/kg was found. Compound 5 expressed the anti-inflammatory action which did not affect the anti-inflammatory activity of diclofenac after their combined administration.

MeSH terms

  • Analgesics / chemical synthesis
  • Analgesics / pharmacology
  • Analgesics / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Carrageenan
  • Drug Eruptions / drug therapy*
  • Drug Synergism
  • Edema / chemically induced
  • Edema / drug therapy
  • Male
  • Mice
  • Morphine / pharmacology
  • Motor Activity / drug effects
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / chemical synthesis
  • Oleanolic Acid / pharmacology
  • Oleanolic Acid / therapeutic use
  • Pain / drug therapy*
  • Rats
  • Rats, Wistar
  • Toxicity Tests, Acute

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • methyl 3-octanoyloxyiminoolean-12-en-28-oate
  • Oleanolic Acid
  • Morphine
  • Carrageenan