Ergosterol and its derivatives from <i>Grifola frondosa</i> inhibit antigen-induced degranulation of RBL-2H3 cells by suppressing the aggregation of high affinity IgE receptors

<i>Grifola frondosa</i> is an edible mushroom consumed as a health food and/or traditional medicine in Asia. However, the anti-allergic effects of <i>G. frondosa</i> are not yet understood. In this study, we demonstrated the effects of <i>G. frondosa</i> extract (GFE) on IgE-mediated allergic responses, using antigen-stimulated RBL-2H3 cells. Three active compounds: ergosterol, 6β-methoxyergosta-7,22-dien-3β,5α-diol (MEDD), and 6-oxoergosta-7,22-dien-3β-ol (6-OXO) were isolated from GFE and shown to inhibit the antigen-induced release of β-hexosaminidase and histamine. Among the three active components, we focused on ergosterol because of its high content in GFE. Ergosterol inhibited the aggregation of high-affinity IgE receptor (FcεRI), which is the first step in the activation of mast cells and antigen-induced tyrosine phosphorylation. Furthermore, ergosterol suppressed antigen-increased IL-4 and TNF-α mRNA. Taken together, our findings suggest that <i>G. frondosa</i>, including ergosterol and its derivatives as active components, has the potential to be a novel functional food that prevents type I allergies.