Anti-allergic actions of F-PASA, a novel herbal cocktail, in IgE/antigen-mediated allergic responses in RBL-2H3 cells and passive cutaneous anaphylaxis in mice

Background: The anti-inflammatory actions of Polygonum cuspidatum, Angelica gigas, Sophora flavescens and Arctium fruit are well known. Nonetheless, effects of herbal combination (PASA) or its fermentation by microorganisms (F-PASA) on the allergic response remain unknown. Purpose: We investigated whether PASA or F-PASA could inhibit IgE/antigen complex (IgE/Ag)-mediated allergic responses. Methods: To evaluate and compare anti-allergic actions of PASA and F-PASA, we performed cell viability, beta-hexosaminidase activity, ELISA assays for cytokines and eicosanoids, immunoblot analysis, HPLC analysis and passive cutaneous anaphylaxis (PCA) models. Results: F-PASA had stronger anti-degranulation actions (IC50, 510.9 mu g/ml) than PASA (IC50, 1,261 mu g/ml) without cytotoxicity until 2000 mu g/ml in IgE/Ag-activated RBL-2H3 cells. Additionally, F-PASA inhibited formation of tumor necrosis factor-alpha (IC50, 147.4 mu g/ml), interleukin-4 (IC50, 213.4 mu g/ml), prostaglandin D2 (IC50, 42.40 mu g/ml) and leukotriene C-4 (IC50, 157.9 mu g/ml). Moreover, F-PASA dose-dependently inhibited the phosphorylation and expression of proteins that are related to the FceRI and arachidonate cascades. Consistent with in vitro studies, F-PASA from 25 to 100 mg/kg also suppressed IgE/Ag-induced PCA reaction more than PASA did in mice. In phytochemical analysis, using PASA and F-PASA, F-PASA showed a higher level of emodin-8-O-beta-D-glucoside, whereas the level of arctiin, an artigenin glycoside, was reduced compared with that using PASA. Conclusion: These findings indicate that F-PASA, including both artigenin and emodin-8-O-beta-D-glucoside, possesses stronger anti-allergic properties. Therefore, F-PASA may be useful as a functional food or as a phytomedicine for allergic diseases.