Damnacanthal inhibits the NF-κB/RIP-2/caspase-1 signal pathway by inhibiting p56lck tyrosine kinase. (October 2014)

• Record Type: Journal Article
• Authors: Kim, Min-Ho; Jeong, Hyun-Ja
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 36:Number 5(2014:Oct.)
• Page Start: 355
• Page End: 363
• Publication Date: 2014-10
• Subjects: Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.3109/08923973.2014.952819
• Languages: English
• ISSNs: 0892-3973

Abstract

<abstract> <title>Abstract</title> <p>Damnacanthal is a major constituent of <italic>Morinda citrifolia L</italic>. (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 p56<sup>lck</sup> 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 p56<sup>lck</sup> 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 p56<sup>lck</sup> tyrosine kinase and suggests that damnacanthal has potential for the treatment of mast cell-mediated allergic disorders.</p> </abstract>