Suppressive effects of britanin, a sesquiterpene compound isolated from Inulae flos, on mast cell-mediated inflammatory responses

Am J Chin Med. 2014;42(4):935-47. doi: 10.1142/S0192415X14500591.

Abstract

Mast cells are central players in immediate-type hypersensitvity and inflammatory responses. In the present study, the effects of britanin on the passive cutaneous anaphylaxis (PCA) reaction in mice and on the phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced production of pro-inflammatory cytokines in human mast cell line (HMC-1) were evaluated. The oral administration of britanin (10-20 mg/kg) decreased the mast cell-mediated PCA reaction in IgE-sensitized mice. In the activity and mechanism of britanin in vitro assay, britanin suppressed the gene expression and secretion of pro-inflammatory cytokines in a dose-dependent manner in HMC-1. In addition, britanin attenuated PMACI-induced activation of NF-κB as indicated by the inhibition of the degradation of IκBα, nuclear translocation of NF-κB, NF-κB/DNA binding activity assay, and blocked the phosphorylation of p38 MAP kinase, in a dose-dependent manner. We conclude that britanin may have potential as a treatment for allergic-inflammatory diseases.

Keywords: Britanin; Mast Cells; Mitogen-Activated Protein (MAP) Kinases; Nuclear Factor (NF)-κB; Passive Cutaneous Anaphylaxis (PCA); Pro-Inflammatory Cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Ophthalmic
  • Animals
  • Calcimycin / pharmacology
  • Calcium Ionophores / pharmacology
  • Cells, Cultured
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Hypersensitivity, Immediate / drug therapy*
  • Hypersensitivity, Immediate / immunology*
  • Inflammation / drug therapy*
  • Inflammation / immunology*
  • Inflammation Mediators / metabolism
  • Inula / chemistry*
  • Lactones / administration & dosage
  • Lactones / isolation & purification
  • Lactones / pharmacology*
  • Male
  • Mast Cells / metabolism*
  • Mice, Inbred ICR
  • NF-kappa B / metabolism
  • Passive Cutaneous Anaphylaxis / drug effects*
  • Passive Cutaneous Anaphylaxis / immunology
  • Phosphorylation / drug effects
  • Phytotherapy*
  • Sesquiterpenes / administration & dosage
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Tetradecanoylphorbol Acetate / analogs & derivatives
  • Tetradecanoylphorbol Acetate / pharmacology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Calcium Ionophores
  • Cytokines
  • Inflammation Mediators
  • Lactones
  • NF-kappa B
  • Sesquiterpenes
  • britannin
  • Calcimycin
  • phorbolol myristate acetate
  • p38 Mitogen-Activated Protein Kinases
  • Tetradecanoylphorbol Acetate