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In this study, we investigated the effect of 3,4,5-trihydroxy-N-(8-hydroxyquinolin-2-yl)benzamide) (SG-HQ2), a synthetic analogue of gallic acid (3,4,5-trihydroxybenzoic acid), on the mast cell-mediated allergic inflammation and the possible mechanism of action. Mast cells play major roles in immunoglobulin E-mediated allergic responses by the release of histamine, lipid-derived mediators, and pro-inflammatory cytokines. We previously reported the potential effects of gallic acid using allergic inflammation models. For incremental research, we synthesized the SG-HQ2 by the modification of functional groups from gallic acid. SG-HQ2 attenuated histamine release by the reduction of intracellular calcium in human mast cells and primary peritoneal mast cells. The inhibitory efficacy of SG-HQ2 was similar with gallic acid. Enhanced expression of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-4, and interleukin-6 in activated mast cells was significantly diminished by SG-HQ2 100 times lower concentration of gallic acid. This inhibitory effect was mediated by the reduction of nuclear factor-κB. In animal models, SG-HQ2 inhibited compound 48/80-induced serum histamine release and immunoglobulin E-mediated local allergic reaction, passive cutaneous anaphylaxis. Our results indicate that SG-HQ2, an analogue of gallic acid, might be a possible therapeutic candidate for mast cell-mediated allergic inflammatory diseases through suppression of histamine release and pro-inflammatory cytokines., (© 2014 by the Society for Experimental Biology and Medicine.)

Mast cell-mediated allergic reaction is involved in many diseases such as asthma and allergic rhinitis. Therefore, discovery of drugs for the prevention or treatment of allergic disease is an important topic in human health. In this study, we evaluated the effects of water extract of Elsholtzia ciliata (Thunb.) Hyland (Labiatae) (WEEC) on mast cell-mediated allergic inflammation and studied the possible mechanisms of action. WEEC inhibited compound 48/80-induced systemic and immunoglobulin E-mediated local anaphylaxis, and serum histamine release in mice. WEEC reduced intracellular calcium levels and downstream histamine release from human mast cells (HMC-1) activated with phorbol 12-myristate 13-acetate and calcium ionophore A23187. In addition, WEEC decreased gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in HMC-1. The inhibitory effect of WEEC on cytokine expression was nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK) dependent. Our results indicate that WEEC inhibits mast cell-mediated allergic inflammatory reactions by suppressing histamine release and proinflammatory cytokine expression, and involvement of calcium, NF-κB and p38 MAPK in these effects.

Allergic disease is a consequence of exposure to normally innocuous substances that elicit the activation of mast cells. Mast-cell-mediated allergic response is involved in many diseases such as anaphylaxis, allergic rhinitis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In this study, we investigated the effect of Lindera obtusiloba water extract (LOWE) on the mast-cell-mediated allergic inflammation and possible mechanism of action using in vitro and in vivo models. LOWE reduced histamine release from various types of mast cells activated by immunoglobulin E (IgE) or phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI). The inhibitory effect of LOWE on histamine release was mediated by calcium signal. LOWE decreased the PMACI-stimulated gene expression of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6 in human mast cells. The inhibitory effect of LOWE on the proinflammatory cytokines was nuclear factor (NF)-κB dependent. In addition, LOWE suppressed compound 48/80-induced systemic allergic reaction and serum histamine release in mice and IgE-mediated local allergic reactions. Our results indicate that LOWE inhibits mast-cell-derived allergic inflammation and involvement of calcium, histamine, proinflammatory cytokines and NF-κB in these effects.