title: Damnacanthal inhibits the NF-κB/RIP-2/caspase-1 signal pathway by inhibiting p56lck tyrosine kinase.
abstract: Damnacanthal is a major constituent of Morinda citrifolia L. (noni) and exhibits anti-cancer and anti-inflammatory activities. However, the effects of damnacanthal on allergic diseases have not been determined. In this study, we investigated the effect of damnacanthal on mast cell-mediated allergic inflammatory responses. Damnacanthal significantly and dose-dependently inhibited compound 48/80-induced systemic anaphylactic shock, histamine release and intracellular calcium levels. In particular, IgE-mediated passive cutaneous anaphylaxis was significantly inhibited by the oral administration of damnacanthal. In addition, we report for the first time that p56lck tyrosine kinase was expressed in phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated mast cells. Furthermore, damnacanthal inhibited the up-regulation of p56lck tyrosine kinase activity by PMACI and repressed PMACI-induced histidine decarboxylase expression and activity. Damnacanthal also inhibited PMACI-induced interleukin (IL)-1β, IL-6 and tumor necrosis factor-α expressions by suppressing nuclear factor-kappa B (NF-κB) activation and suppressed the activation of caspase-1 and the expression of receptor interacting protein-2. This study shows damnacanthal inhibits the NF-κB/receptor-interacting protein-2/caspase-1 signal pathway by inhibiting p56lck tyrosine kinase and suggests that damnacanthal has potential for the treatment of mast cell-mediated allergic disorders.
authors.affiliation: High-Enthalpy Plasma Research Center, Chonbuk National University , Jeonju , Republic of Korea and.
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Kim
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D020170:Caspase 1 / Q000187:drug effects*; D061945:Caspase Inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000037:antagonists & inhibitors*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D003189:p-Methoxy-N-methylphenethylamine
chemical_list: D000880:Anthraquinones; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D003189:p-Methoxy-N-methylphenethylamine; C079170:damnacanthal; D011505:Protein-Tyrosine Kinases; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse; D020170:Caspase 1
keywords: Allergic response; damnacanthal; histidine decarboxylase; p56lck tyrosine kinasecaspase-1