METHODS: Xanthopurpurin (XPP) compound was isolated and identified, and its anti-IgE effect was tested in human B cell line and PBMCs from food allergic subjects. Peanut-allergic C3H/HeJ mice were intragastrically treated with XPP at 200µg or 400µg per mouse daily, or received sham treatment. Serum peanut-specific IgE levels, hypersensitivity reactions following peanut challenge, splenocyte cytokine levels, and spleen and bone marrow IgE + B cells were assessed. RNASeq and qPCR were employed to determine the regulatory genes of IgE by XPP.
RESULTS: XPP significantly and dose-dependently inhibited IgE production in vitro. XPP treatment significantly reduced anaphylaxis scores compared to shame treated peanut allergic mice in both early and late treatment experiments (p<0.05-p<0.001, n=10-20), associated with significant reduction of plasma histamine levels. It reduced peanut-specific IgE levels by 80% (p<0.01), associated with significant reduction of IL-4 without affecting IgG, IgA or IFN-γ production. XPP showed strong post-therapy protection at least 5 weeks after the treatment. The flow cytometry data revealed that XPP reduced peripheral and bone marrow IgE + B cells compared to the untreated group. XBP-1 was identified as one of the important transcription factors associated with XPP suppression of IgE.
CONCLUSIONS: XPP inhibits IgE production both in vitro and in vivo and might be a novel therapy for IgE-mediated food allergy.