Alisol B 23-Acetate Inhibits IgE/Ag-Mediated Mast Cell Activation and Allergic Reaction

Int J Mol Sci. 2018 Dec 18;19(12):4092. doi: 10.3390/ijms19124092.

Abstract

Alisol B 23-acetate (AB23A), a natural triterpenoid, has been reported to exert hepatoprotective and antitumor activities. Aiming to investigate the anti-inflammatory activity, this study examined the effect of AB23A on mast cells and allergic reaction. AB23A inhibited the degranulation of mast cells stimulated by immunoglobulin E/antigen (IgE/Ag), and also decreased the synthesis of leukotriene C₄ (LTC₄), production of interlukin-6 (IL-6), and expression of cyclooxygenase-2 (COX-2) in a concentration-dependent manner with no significant cytotoxicity in bone marrow-derived mast cells (BMMCs). AB23A inhibited spleen tyrosine kinase (Syk) and the downstream signaling molecules including phospholipase Cγ (PLCγ), serine-threonine protein kinase/inhibitor of nuclear factor kappa-B kinase/nuclear factor kappa-B (Akt/IKK/NF-κB), and mitogen-activated protein kinases/cytosolic phospholipase A₂ (MAPK/cPLA₂). Furthermore, AB23A blocked mobilization of Ca2+. Similar results were obtained in other mast cell lines Rat basophilic leukemia (RBL)-2H3 cells and a human mast cell line (HMC-1). In addition, AB23A attenuated allergic responses in an acute allergy animal model, passive cutaneous anaphylaxis (PCA). Taken together, this study suggests that AB23A inhibits the activation of mast cells and ameliorates allergic reaction, and may become a lead compound for the treatment of mast cell-mediated allergic diseases.

Keywords: AB23A; IgE; PCA; mast cell.

MeSH terms

  • Animals
  • Anti-Allergic Agents / pharmacology*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology
  • Cell Degranulation / drug effects
  • Cholestenones / pharmacology*
  • Humans
  • Hypersensitivity / drug therapy*
  • Hypersensitivity / immunology
  • Hypersensitivity / pathology
  • Immunoglobulin E / immunology
  • Leukotriene C4 / biosynthesis
  • Mast Cells / drug effects*
  • Mast Cells / immunology
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Phospholipase C gamma / genetics
  • Protein Serine-Threonine Kinases / genetics
  • Rats
  • Spleen / drug effects
  • Spleen / enzymology
  • Syk Kinase

Substances

  • Anti-Allergic Agents
  • Cholestenones
  • alisol B 23-acetate
  • Leukotriene C4
  • Immunoglobulin E
  • Syk Kinase
  • Protein Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • Phospholipase C gamma