Sustained silencing peanut allergy by xanthopurpurin is associated with suppression of peripheral and bone marrow IgE producing B cell

RATIONALE: IgE play a key role in mediating peanut anaphylaxis. The herbal medicine Rubia cordifolia L. inhibits IgE production in vitro and in vivo. This study was to identify IgE inhibitory compound from Rubia cordifolia L. and investigate underlying mechanisms.

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.