title: Damnacanthal inhibits IgE receptor-mediated activation of mast cells.
abstract: Damnacanthal, an anthraquinone obtained from the noni fruit (Morinda citrifolia L.), has been described to possess anti-cancer and anti-inflammatory properties. Since mast cells are key players in various inflammatory conditions as well as in cancer, we considered the possibility that the biological actions of damnacanthal, at least partly, could be due to effects on mast cells. Many of the biological activities of mast cells are mediated by IgE receptor cross-linking, which results in degranulation with release of preformed granule mediators, as well as de novo synthesis and release of additional compounds. Here we show that damnacanthal has profound inhibitory activity on mast cell activation through this pathway. The release of the granule compounds beta-hexosaminidase and tryptase release was completely abrogated by damnacanthal at doses that were non-toxic to mast cells. In addition, damnacanthal inhibited activation-dependent pro-inflammatory gene induction, as well as cytokine/chemokine release in response to mast cell stimulation. The mechanism underlying damnacanthal inhibition was linked to impaired phosphorylation of Syk and Akt. Furthermore, damnacanthal inhibited mast cell activation in response to calcium ionophore A23187. Altogether, the data presented here demonstrate that damnacanthal inhibits mast cell activation induced by different stimuli and open a new window for the use of this compound as a mast cell stabilizer.
authors: Universidad de Málaga, Andalucía Tech, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, and IBIMA (Biomedical Research Institute of Málaga); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga, Spain.
authors: Javier A
authors: JA
authors: Garcia-Vilas
authors: Universidad de Málaga, Andalucía Tech, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, and IBIMA (Biomedical Research Institute of Málaga); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga, Spain.
authors: Miguel A
authors: MA
authors: Medina
authors: Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry, Uppsala, Sweden.
authors: Fabio R
authors: FR
authors: Melo
authors: Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry, Uppsala, Sweden; Uppsala University, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden.
authors: Gunnar
authors: G
authors: Pejler
authors: Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry, Uppsala, Sweden. Electronic address: gianni.garcia@slu.se.
authors: Gianni
authors: G
authors: Garcia-Faroldi
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017455:Receptors, IgE / Q000037:antagonists & inhibitors*; D000072377:Syk Kinase; D053802:Tryptases / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; D000001:Calcimycin; C079170:damnacanthal; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D001619:beta-N-Acetylhexosaminidases; D053802:Tryptases
keywords: Activation; Cytokines; Damnacanthal; Degranulation; IgE-R-cross-linking; Mast cell