1,6-O,O-Diacetylbritannilactone suppresses activation of mast cell and airway hyper-responsiveness

Immunopharmacol Immunotoxicol. 2017 Aug;39(4):173-179. doi: 10.1080/08923973.2017.1318911. Epub 2017 Apr 27.

Abstract

Mast cells play critical roles in allergic disorders such as atopic dermatitis and allergic asthma. The aim of this study was to investigate the anti-inflammatory and anti-asthmatic activities of 1,6-O,O-diacetylbritannilactone (OODBL) isolated from Inula japonica Thunb. (I. japonica) in a murine asthma model and bone marrow-derived mast cells (BMMCs). In an ovalbumin-induced asthma model, OODBL administration attenuated the airway hyper-responsiveness induced by aerosolized methacholine and serum IgE level in asthmatic mice. In vitro system, we found that OODBL reduced leukotriene C4 production and degranulation through the suppression of cytosolic phospholipase A2 phosphorylation and phospholipase Cγ-mediated Ca2+ influx in IgE/antigen-stimulated BMMCs. Taken together, OODBL may have therapeutic potential in the treatment of allergic diseases such as asthma.

Keywords: OODBL; asthma; inflammation; leukotriene C4; mast cell degranulation.

MeSH terms

  • Animals
  • Anti-Allergic Agents / pharmacology
  • Anti-Asthmatic Agents / pharmacology
  • Anti-Inflammatory Agents / pharmacology
  • Asthma / chemically induced
  • Asthma / drug therapy
  • Asthma / metabolism
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cell Degranulation / drug effects
  • Dermatitis, Atopic / chemically induced
  • Dermatitis, Atopic / drug therapy
  • Dermatitis, Atopic / metabolism
  • Disease Models, Animal
  • Female
  • Immunoglobulin E / metabolism
  • Lactones / pharmacology*
  • Leukotriene C4 / metabolism
  • Mast Cells / drug effects*
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / pharmacology
  • Phosphorylation / drug effects
  • Respiratory Hypersensitivity / chemically induced
  • Respiratory Hypersensitivity / drug therapy*
  • Respiratory Hypersensitivity / metabolism
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Anti-Allergic Agents
  • Anti-Asthmatic Agents
  • Anti-Inflammatory Agents
  • Lactones
  • O, O-diacetylbritannilactone
  • Sesquiterpenes
  • Leukotriene C4
  • Immunoglobulin E
  • Ovalbumin