ABSTRACT
The discovery of drugs for the treatment of allergic disease is an important subject in human health. Stimulation of mast cells starts the process of degranulation resulting in releasing of mediators, such as histamine. In this report, we investigated the effect of aqueous extract of Dracocephalum argunense Fisch. (Labiatae) (DAAE) on the mast cell-mediated allergic response and studied its possible mechanisms of action, focusing on the histamine release and pro-inflammatory cytokine secretion in mast cells. DAAE inhibited compound 48/80-induced systemic reactions and serum histamine release in mice. In addition, DAAE attenuated IgE-mediated skin allergic reaction. DAAE dose-dependently reduced IgE-induced histamine release from mast cells. The level of cAMP was transiently increased by treatment of DAAE. DAAE specifically blocked the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-induced p38 mitogen-activated protein kinase (MAPK) activation. DAAE decreased the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 in mast cells. Our findings provide evidence that DAAE inhibits mast cell derived allergic reactions, and involvement of cAMP for histamine release and p38 MAPK for pro-inflammatory cytokine secretion in these effects.
Subject(s)
Anti-Allergic Agents , Hypersensitivity/drug therapy , Hypersensitivity/immunology , Lamiaceae/chemistry , Mast Cells/drug effects , Mast Cells/immunology , Anaphylaxis/chemically induced , Anaphylaxis/prevention & control , Animals , Blotting, Western , Calcimycin/pharmacology , Cyclic AMP/metabolism , Histamine Release/drug effects , Immunoglobulin E/biosynthesis , Immunoglobulin E/genetics , Interleukin-6/metabolism , Male , Mice , Mice, Inbred ICR , Passive Cutaneous Anaphylaxis/drug effects , Rats , Rats, Sprague-Dawley , Tetradecanoylphorbol Acetate/pharmacology , Tumor Necrosis Factor-alpha/metabolism , p-Methoxy-N-methylphenethylamine/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
The immediate-type allergic reaction (anaphylaxis) is involved in many allergic diseases such as asthma, allergic rhinitis and sinusitis. We investigated the effect of the gall of Rhus javanica (GRJ) on the model of the immediate-type allergic reaction, and studied its possible mechanisms. GRJ inhibited compound 48/80-induced systemic reactions in mice. GRJ attenuated immunoglobulin (Ig) E-mediated local allergic reactions. In addition, GRJ dose dependently decreased histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. The decreasing effect of GRJ on the histamine release was mediated by the modulation of cAMP and [Ca2+]i in mast cells. Furthermore, GRJ decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated TNF-alpha and IL-6 secretion in human mast cells. The inhibitory effect of GRJ on the pro-inflammatory cytokine was c-Jun N-terminal kinase and nuclear factor-kappaB dependent. Our findings provide evidence that GRJ inhibits mast cell-derived immediate-type allergic reactions, and suggest the possible mechanisms of action.
