Salvinorin A inhibits ovalbumin‐stimulated allergic rhinitis and RBL‐2H3 cells degranulation

Allergic rhinitis (AR) is a long-term noncommunicable inflammatory disease of the nasal mucosa mediated by immunoglobulin E and is mainly caused by exposure of genetically susceptible individuals to environmental allergens. Mast cells contribute to the pathogenesis of allergic and nonallergic inflammatory diseases. Salvinorin A has been previously shown to inhibit leukotriene production and mast cell degranulation to suppress airway hyperresponsiveness caused by sensitization; thus, we hypothesized that salvinorin A has an anti-AR effect. We tested this hypothesis using monoclonal anti-2,4,6-dinitrophenyl immunoglobulin E/human serum albumin-induced rat basophilic leukemia cells (RBL-2H3 cells) and ovalbumin (OVA)-induced AR in mice as in vivo and in vitro AR models, respectively. The expression levels of histamine, β-hexosaminidase, interleukin-4 and tumor necrosis factor-α were decreased by salvinorin A in vitro. Granule release and F-actin organization were also suppressed by salvinorin A. Furthermore, salvinorin A inhibited OVA-induced features of AR in mice, including nasal rubbing and sneezing, as well as increased OVA-specific immunoglobulin E, histamine, tumor necrosis factor-α and interleukin-4 levels. In addition, salvinorin A decreased the phosphorylation of phosphoinositide 3-kinase/Akt in vitro and in vivo. Our work suggests that salvinorin A suppresses AR caused by sensitization by inhibiting the inflammatory responses of mast cells; thus, salvinorin A may have potential for treatment of AR.