Macelignan inhibits histamine release and inflammatory mediator production in activated rat basophilic leukemia mast cells

Inflammation. 2012 Oct;35(5):1723-31. doi: 10.1007/s10753-012-9490-1.

Abstract

Type I allergy is characterized by the release of granule-associated mediators, lipid-derived substances, cytokines, and chemokines by activated mast cells. To evaluate the anti-allergic effects of macelignan isolated from Myristica fragrans Houtt., we determined its ability to inhibit calcium (Ca(2+)) influx, degranulation, and inflammatory mediator production in RBL-2 H3 cells stimulated with A23187 and phorbol 12-myristate 13-acetate. Macelignan inhibited Ca(2+) influx and the secretion of β-hexosaminidase, histamine, prostaglandin E(2), and leukotriene C(4); decreased mRNA levels of cyclooxygenase-2, 5-lipoxygenase, interleukin-4 (IL-4), IL-13, and tumor necrosis factor-α; and attenuated phosphorylation of Akt and the mitogen-activated protein kinases extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase. These results indicate the potential of macelignan as a type I allergy treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Arachidonate 5-Lipoxygenase / genetics
  • Calcimycin
  • Calcium / metabolism
  • Cell Degranulation / drug effects
  • Cell Line, Tumor
  • Cyclooxygenase 2 / genetics
  • Dinoprostone / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Histamine Release / drug effects*
  • Hypersensitivity / drug therapy*
  • Inflammation Mediators / metabolism*
  • Interleukin-13 / genetics
  • Interleukin-4 / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Leukemia, Basophilic, Acute / metabolism
  • Leukotriene C4 / metabolism
  • Lignans / pharmacology*
  • Lignans / therapeutic use
  • Mast Cells / drug effects
  • Mast Cells / immunology*
  • Mast Cells / metabolism*
  • Myristica
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Tetradecanoylphorbol Acetate
  • Tumor Necrosis Factor-alpha / genetics
  • beta-N-Acetylhexosaminidases / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Inflammation Mediators
  • Interleukin-13
  • Lignans
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Leukotriene C4
  • Calcimycin
  • macelignan
  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 2
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • beta-N-Acetylhexosaminidases
  • Dinoprostone
  • Tetradecanoylphorbol Acetate
  • Calcium