The discovery of drugs for the treatment of inflammatory allergic diseases such as, asthma, allergic rhinitis, and sinusitis is a very important subject in human health. Gallic acid (3,4,5-trihydroxybenzoic acid), a polyphenyl natural products from gallnut and green tea, is known to have anti-oxidant, anti-inflammatory, anti-microbial, and radical scavenging activities. The aim of the present study was to elucidate whether gallic acid modulates the inflammatory allergic reaction and to study its possible mechanisms of action. Gallic acid attenuated compound 48/80- or immunoglobulin E (IgE)-induced histamine release from mast cells. The inhibitory effect of gallic acid on the histamine release was mediated by the modulation of cAMP and intracellular calcium. Gallic acid decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated pro-inflammatory cytokine gene expression and production such as TNF-alpha and IL-6 in human mast cells. The inhibitory effect of gallic acid on the pro-inflammatory cytokine was nuclear factor-kappaB and p38 mitogen-activated protein kinase dependent. In addition, gallic acid inhibited compound 48/80-induced systemic allergic reaction and IgE-mediated local allergic reaction. The inhibitory activity of gallic acid on the allergic reaction and histamine release was found to be similar with disodium cromoglycate. Our findings provide evidence that gallic acid inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression, and suggest the mechanisms of action. Furthermore, in vivo and in vitro anti-allergic effect of gallic acid suggests a possible therapeutic application of this agent in inflammatory allergic diseases.

Five compounds were isolated from the chloroform-soluble fraction of the methanolic extract of the dried rhizomes of Zingiber officinale (Zingiberaceae) through repeated column chromatography. Their chemical structures were elucidated as 4-, 6-, 8-, and 10-gingerols, and 6-shogaol using spectroscopic analysis. Among the five isolated compounds, 6-shogaol exhibited the most potent cytotoxicity against human A549, SK-OV-3, SK-MEL-2, and HCT15 tumor cells. 6-shogaol inhibited proliferation of the transgenic mouse ovarian cancer cell lines, C1 (genotype: p53(-/-), c-myc, K-ras) and C2 (genotype: p53(-/-), c-myc, Akt), with ED(50) values of 0.58 microM (C1) and 10.7 microM (C2).

Lipopolysaccharide (LPS) produces reactive oxygen species (ROS) and nitric oxide (NO) in macrophages. These molecules are involved in inflammation associated with endotoxic shock. Selenium (Se), a biologically essential trace element, modulates the functions of many regulatory proteins involved in signal transduction and affects a variety of cellular activities, including cell growth and survival. We demonstrate that Se attenuated LPS-induced ROS and NO production in murine macrophage cultures in vitro. This Se-decreased production of NO was demonstrated by decreases in both mRNA and protein expression for inducible NO synthase (iNOS). The preventive effects of Se on iNOS were p38 mitogen-activated protein kinase- and nuclear factor-kappaB-dependent. Se specifically blocked the LPS-induced activation of p38 but not that of c-jun-N-terminal kinase and extracellular signal-regulated kinase; the p38-specific pathway was confirmed using p38 inhibitor SB 203580. These results suggest that the mechanism by which Se may act as an anti-inflammatory agent and that Se may be considered as a possible preventive intervention for endotoxemia, particularly in Se-deficient locations. However, the efficacy and safety of Se need to be further investigated, because long-term intake > 0.4 mg Se/day in adults can produce adverse effects.

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Background: Epigallocatechin-3-gallate (EGCG) is a major form of tea catechin and has a variety of biological activities. In the present study, we investigated the effect of EGCG on the secretion of TNF-α, IL-6 and IL-8, as well as its possible mechanism of action by using the human mast cell line (HMC-1). Methods: EGCG was treated before the activation of HMC-1 cells with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore (A23187). To investigate the effect of EGCG on PMA+A23187-stimulated HMC-1 cells, ELISA, Western blot analysis, electrophorectic mobility shift assay and luciferase assay were used in this study. Results: EGCG (100 µM) inhibited PMA+A23187-induced TNF-α, IL-6 and IL-8 expression and production. EGCG inhibited the intracellular Ca²⁺ level. EGCG attenuated PMA+A23187-induced NF-ĸB and extracellular signal-regulated kinase (ERK1/2) activation, but not that of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. Conclusion: EGCG inhibited the production of TNF-α, IL-6 and IL-8 through the inhibition of the intracellular Ca²⁺ level, and of ERK1/2 and NF-ĸB activation. These results indicate that EGCG may be helpful in regulating mast-cell-mediated allergic inflammatory response.

The discovery of drugs for the treatment of allergic disease is an important subject in human health. The Artemisia iwayomogi (Compositae) (AIE) has been used as a traditional medicine in Korea and is known to have an anti-inflammatory effect. However, its specific mechanism of action is still unknown. In this report, we investigated the effect of AIE on the mast cell-mediated allergy model and studied the possible mechanism of action. AIE inhibited compound 48/80-induced systemic reactions and plasma histamine release in mice. AIE decreased immunoglobulin E (IgE)-mediated local allergic reaction, passive cutaneous anaphylaxis (PCA) reaction. AIE dose dependently attenuated histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. AIE decreased the compound 48/80-induced intracellular Ca(2+). Furthermore, AIE decreased the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated tumor necrosis factor-alpha and interleukin-6 gene expression and production in human mast cells. The inhibitory effect of AIE on the proinflammatory cytokine was p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) dependent. AIE attenuated PMA plus A23187-induced degradation of IkappaBalpha and nuclear translocation of NF-kappaB and specifically blocked activation of p38 MAPK but not that of c-jun N-terminal kinase and extracellular signal-regulated kinase. Our findings provide evidence that AIE inhibits mast cell-derived immediate-type allergic reactions and involvement of intracellular Ca(2+), proinflammatory cytokines, p38 MAPK, and NF-kappaB in these effects.

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