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Dracocephalum argunense FISCH. (Labiatae) (DAAE) has been used for centuries as traditional oriental medicine. This crude drug is used for the management of pulmonary phthisis, abdominal phthisis, hepatitis and gastritis. 1) Mast cells, which are constituents of virtually all organs and tissue, are important mediators of inflammatory responses such as allergy and hypersensitivity. Immediate-type hypersensitivity, anaphylaxis, is mediated by histamine release in response to antigen cross-linking of immunoglobulin E (IgE) bound to FceRI on mast cells. Mast cell activation causes the process of degranulation that result in releasing of mediators, such as histamine. [2][3][4] Among the inflammatory substances released from mast cells, histamine remains the best-characterized and most potent vasoactive mediator implicated in the acute phase of immediate hypersensitivity.5) Mast cell activation is initiated upon interaction of multivalent antigen with its specific IgE antibody attached to the cell membrane via FceRI.6,7) Antidinitrophenyl (DNP) IgE antibody and antigen have been established to induce passive cutaneous anaphylaxis (PCA) reactions as a typical in vivo model for immediate hypersensitivity. Mast cell degranulation also can be elicited by nonimmunologic stimulators such as neuropeptides, basic compounds, complement components, and certain drugs.8) Compound 48/80 and polymers of basic amino acids, such as substance P, are some of the most potent stimulators of mast cells.9) Thus, an appropriate amount of compound 48/80 has been used as a direct and convenient reagent to study the mechanism of anaphylactic allergic reaction.The signaling pathway leading to degranulation of mast cells after engagement of the FceRI receptor has been extensively characterized.3,10) Activation of mast cells leads to phosphorylation of tyrosine kinase and mobilization of internal calcium. This is followed by activation of protein kinase C, mitogen-activated protein kinase (MAPK), and releasing of inflammatory cytokines. Although mast cells also store small amounts of cytokines in their granules, these cells dramatically increase the production of tumor necrosis factor-a (TNF-a), interleukin (IL)-6 and other cytokines after their surface FceRI are cross-linked with specific antigen. [11][12][13][14] In this study, we evaluated the effect of DAAE on the compound 48/80-induced systemic reaction, IgE-mediated local allergic reaction, and histamine release from mast cells. The cAMP level was investigated to clarify the mechanism by which DAAE inhibited histamine release from mast cells. In addition, the effect of DAAE on phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-induced TNFa and IL-6 secretion, and role of MAPK in this effect were investigated in human mast cells (HMC-1). MATERIALS AND METHODS Reagents and Cell CultureCompound 48/80, anti-DNP IgE, DNP-human serum albumin (HSA), o-phthaldialdehyde, PMA, calcium ionophore A23187, and metrizamide were purchased from Sigma (St. Louis, MO, U.S.A.). SB 203580 was p...

The immediate-type allergic reaction is involved in many allergic diseases such as asthma, allergic rhinitis, and sinusitis. The discovery of drugs for the treatment of immediate-type allergic disease is a very important subject in human health. The formulated ethanol extract of Artemisia asiatica Nakai (DA-9601) has been reported to have antioxidative and anti-inflammatory activities. In this report, we investigated the effect of DA-9601 on the immediatetype allergic reaction and studied its possible mechanisms of action, focusing on the mast cell-mediated allergic reaction. DA-9601 inhibited compound 48/80-induced systemic anaphylactic reactions and serum histamine release in mice. DA-9601 decreased the IgE-mediated passive cutaneous anaphylaxis, the model of local allergic reaction in vivo. DA-9601 dose-dependently reduced histamine release from mast cells activated by compound 48/80 or IgE. Furthermore, DA-9601 decreased the gene expression and production of tumor necrosis factor (TNF)-α in phorbol 12-myristate 13-acetate plus A23187-stimulated mast cells. These findings provide evidence that DA-9601 could be a candidate as an anti-allergic agent.