Gallic Acid Inhibits Histamine Release and Pro-inflammatory Cytokine Production in Mast Cells

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.