Effect of Dracocephalum argunense on mast-cell-mediated hypersensitivity.
BACKGROUND
Stimulation of mast cells starts the process of degranulation resulting in release of mediators such as histamine and an array of inflammatory cytokines. In this report, we investigated the effect of an aqueous extract of Dracocephalum argunense Fisch. (Labiatae) (DAAE) on immediate-type hypersensitivity and studied its possible mechanisms of action, focusing on histamine release and proinflammatory cytokine expression in mast cells.


METHODS
An in vivo model of systemic and local allergic reaction was investigated. Compound 48/80- or IgE-induced histamine release from mast cells was measured. The expression of proinflammatory cytokines such as TNF-alpha and IL-6 was measured by RT-PCR and ELISA. The level of intracellular calcium was measured by spectrofluorometry. NF-kappaB activation was measured by Western blot, EMSA and luciferase assay.


RESULTS
DAAE inhibited systemic anaphylaxis, local allergic reactions, and serum histamine release in a dose-dependent manner in mice. DAAE dose-dependently reduced histamine release from mast cells activated by compound 48/80 or IgE. The inhibitory effect of DAAE on histamine release was mediated by the modulation of intracellular calcium. In addition, DAAE decreased TNF-alpha and IL-6 gene expression and production in human mast cells stimulated by phorbol-12-myristate-13-acetate (PMA) plus calcium ionophore A23187. The inhibitory effect of DAAE on the TNF-alpha and IL-6 expression was NF-kappaB dependent.


CONCLUSIONS
Our findings provide evidence that DAAE inhibits mast-cell-derived immediate-type hypersensitivity. Taken together, the anti-allergic effect of DAAE in vivo and in vitro suggests a possible clinical use of this agent in immediate-type hypersensitivity.
Kim
Sang-Hyun
SH
Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Shin
Tae-Yong
TY
D000707:Anaphylaxis / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D002118:Calcium / Q000032:analysis; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D019686:Lamiaceae / Q000737:chemistry*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium