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

Abstract

Grifola frondosa is an edible mushroom consumed as a health food and/or traditional medicine in Asia. However, the anti-allergic effects of G. frondosa are not yet understood. In this study, we demonstrated the effects of G. frondosa 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 G. frondosa, including ergosterol and its derivatives as active components, has the potential to be a novel functional food that prevents type I allergies.

Bioactive compounds from an endophytic fungi Nigrospora aurantiaca

“…Through chemical investigation of the liquid and solid fermented products, one new compound together with five known compounds on N. aurantiaca (an endophytic fungi from M. leucadendra ) were identified. By comparing with literature data, the well-known compounds were recognized as xyloketal K ( 2 ) (Sun et al 2016 ), bostrycin ( 3 ) (Stevens et al 1979 ; Chen et al 2012 ), deoxybostrycin ( 4 ) (Chen et al 2012 ; Wang et al 2013 ), xylanthraquinone ( 5 ) (Sommart et al 2008 ), and ergosterol ( 6 ) (Kawai et al 2018 ).…”

Suppression of leukotriene B 4 production is involved in the anti-pruritic action of Grifola frondosa in pollen allergy-induced ocular itching in mice

“…IgE-mediated mast cell activation induces LTB 4 production (Miyahara et al, 2009;Yamashita et al, 2000). As a possible mechanism, our recent study demonstrated that ergosterol inhibits the antigen-induced aggregation of highaffinity IgE receptors on mast cells (Kawai et al, 2018). Therefore, the inhibition of high-affinity IgE receptor aggregation by ergosterol may be involved in the regulation of LTB 4 production.…”

“…The mouse model of immediate pollen allergy-induced ocular itching used in this study critically depends on mast cells (Andoh et al, 2012). Recent reports have shown that G. frondosa extracts and ergosterol inhibit the antigen-induced histamine release of mast cells, and the oral administration of G. frondosa extracts or ergosterol inhibits antigen-induced allergic responses by suppressing histamine release in mast cells in mice (Kawai et al, 2018;Kawai et al, 2019). Histamine is partly involved in pollen allergy-induced ocular itching (Andoh et al, 2012).…”

“…In addition, it was recently reported that G. frondosa exhibits anti-allergic activity (Park et al, 2015). In our previous study, G. frondosa extract, its active component ergosterol, and its derivatives inhibited antigen-induced activation, including degranulation and histamine release, in the rat basophilic leukemia cell line RBL-2H3 (Kawai et al, 2018). Furthermore, oral administration of G. frondosa extract or ergosterol suppressed allergic reactions in ovalbumin-sensitized mice (Kawai et al, 2019).…”

Structure and Biological Activity of Ergostane-Type Steroids from Fungi

“…Its treatment of RAW 264.7 macrophages inhibited lipopolysaccharide-induced inflammation by suppressing the production of tumor necrosis factor-α and expression of cyclooxygenase-2 [ 46 ]. The inhibitory effect of ergosterol on degranulation of mucosal-type murine bone marrow-derived mast cells [ 47 ] or basophilic leukemia (RBL-2H3) cells [ 48 ] was associated with inhibition of β-hexosaminidase and histamine release in antigen-stimulated cells and was of interest for the treatment of allergic diseases dependent on mast cells.…”