New insight into the inhibition of the inflammatory response to experimental delayed-type hypersensitivity reactions in mice by scropolioside A

Eur J Pharmacol. 2007 Jan 26;555(2-3):199-210. doi: 10.1016/j.ejphar.2006.10.012. Epub 2006 Oct 17.

Abstract

Scropolioside A, an iridoid isolated from Scrophularia auriculata ssp. pseudoauriculata, showed anti-inflammatory properties against different experimental models of delayed-type hypersensitivity. This iridoid reduced the oedema induced by oxazolone by 79% (72 h) at 0.5 mg/ear while reducing that induced by sheep red blood cells by 47% (18 h), 45% (24 h) and 36% (48 h) at 10 mg/kg. In vivo it reduced both oedema formation and cell infiltration whereas in vitro it reduced the proliferation of activated T-lymphocytes (IC50 of 67.74 microM). Treatment with scropolioside A (100 microM) 18 and 24 h after phytohemagglutinin stimulation increased the number of cells arrested in the subG(0) phase whereas treatment 3 h after stimulation clearly increased the number of cells that passed to the S phase. Scropolioside A also inhibited the production of prostaglandin E2, leukotriene B4, nitric oxide, interleukin-1beta, interleukin-2, interleukin-4, tumour necrosis factor-alpha and interferon-gamma, but had no effect on the production of interleukin-10. Moreover, it modified the expression of both nitric oxide synthase-2 and cyclooxygenase-2, as well as the activation of nuclear factor-kappaB in RAW 264.7 macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Line
  • Cytokines / biosynthesis
  • Dinoprostone / immunology
  • Ear / pathology
  • Edema / chemically induced
  • Erythrocytes / immunology
  • Female
  • Glucosides / pharmacology*
  • Humans
  • Hypersensitivity, Delayed / chemically induced
  • Hypersensitivity, Delayed / drug therapy
  • Hypersensitivity, Delayed / immunology
  • Hypersensitivity, Delayed / pathology
  • Leukotriene B4 / immunology
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Oxazolone
  • Pancreatic Elastase / immunology
  • Pyrans / pharmacology*
  • Sheep
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Allergens
  • Anti-Inflammatory Agents
  • Cytokines
  • Glucosides
  • Lipopolysaccharides
  • Pyrans
  • scropolioside A
  • Oxazolone
  • Leukotriene B4
  • Pancreatic Elastase
  • Caspase 3
  • Dinoprostone