Warifteine, a bisbenzylisoquinoline alkaloid, decreases immediate allergic and thermal hyperalgesic reactions in sensitized animals

Int Immunopharmacol. 2008 Apr;8(4):519-25. doi: 10.1016/j.intimp.2007.11.009. Epub 2007 Dec 26.

Abstract

Warifteine is a bisbenzylisoquinoline alkaloid isolated from the Cissampelos sympodialis Eichl (Menispermaceae). This plant is used in the folk medicine for the treatment of airway respiratory diseases. A murine model of immediate allergic reaction was used to evaluate warifteine treatment in the IgE production, leukocyte activation, thermal hyperalgesia, mast cell degranulation and scratching behavior. BALB/c mice treated with warifteine (0.4-10 mg/Kg) 1 h before OVA sensitization reduced OVA induced paw edema as well as the OVA-specific IgE serum titers as compared with non-treated and OVA-sensitized animals. Warifteine also reduced the mice death evoked by IgE-dependent anaphylactic shock reaction at 30 min after intravenous OVA challenge. To assess the effect of warifteine treatment on T cell proliferative response, spleen cells from warifteine treated or non-treated and OVA-sensitized animals were evaluated. Spleen cells from warifteine treated animals (2.0 mg/kg) did not proliferate following OVA stimulation as compared with spleen cell cultures from non-treated animals. This response may be related with the increase of NO production as observed in peritoneal macrophage cultures treated with warifteine. Thermal hyperalgesia evoked by IgE or histamine/5-hydroxytryptamine challenge was inhibited on rats at dose of 4.0 mg/kg. Warifteine treatment (0.6 or 6.0 microg/ml) also decreased the IgEalphaDNP-BSA sensitized mast degranulation after DNP-BSA challenge measured by histamine release. In addition, compound 48/80-induced scratching behavior was also sensitive to warifteine treatment. These results demonstrate for the first time that warifteine treatment reduced the allergy-associated responses.

MeSH terms

  • Alkaloids / administration & dosage
  • Alkaloids / isolation & purification
  • Alkaloids / therapeutic use*
  • Anaphylaxis / drug therapy
  • Anaphylaxis / immunology
  • Animals
  • Cell Degranulation / drug effects
  • Cell Proliferation / drug effects
  • Drug Evaluation, Preclinical
  • Histamine Release / drug effects
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / immunology
  • Hypersensitivity, Immediate / drug therapy*
  • Immunoglobulin E / blood
  • Lymphocyte Activation / drug effects
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / metabolism
  • Ovalbumin / immunology
  • Rats
  • Rats, Wistar
  • T-Lymphocytes / immunology*

Substances

  • Alkaloids
  • Nitric Oxide
  • Immunoglobulin E
  • warifteine
  • Ovalbumin