Ethyl acetate extract of Psidium guajava']java inhibits IgE-mediated allergic responses by blocking FcεRI signaling

Psidium guajava (P. guajava) is an important food crop and medicinal plant with antioxidant, anti-inflammatory, and anti-allergic activities, supporting its traditional uses. However, its precise effects remain unknown. We investigated the effects of P. guajava ethyl acetate extract (PGEA) on IgE-mediated allergic responses in rat mast RBL-2H3 cells. PGEA reduced antigen (DNP-BSA)-induced release of beta-hexosaminidase and histamine in IgE-sensitized RBL-2H3 cells. In addition, it inhibited antigen-induced IL-4 and TINIF-alpha mRNA expression and protein production in IgE-sensitized RBL-2H3 cells. PGEA also suppressed antigen-induced COX-2 mRNA and protein expression in these cells, as well as antigen-induced activation of NFAT and reactive oxygen species. Moreover, it inhibited antigen-induced activation of NF-kappa B and degradation of I kappa B-alpha. To identify the mechanisms underpinning the inhibition of degranulation and cytokine production by PGEA, we examined the activation of intracellular Fc epsilon RI signaling molecules. PGEA suppressed antigen-induced phosphorylation of Syk, LAT, Gab2, and PLC gamma 2 but not Lyn, and inhibited antigen-induced phosphorylation of downstream signaling intermediates including MAP kinases and Akt. Collectively, the anti-allergic effects of PGEA in vitro suggest its possible therapeutic application to inflammatory allergic diseases, in which its inhibition of inflammatory cytokine production and Fc epsilon RI-dependent signaling events in mast cells may be hugely beneficial. (c) 2010 Elsevier Ltd. All rights reserved.