Inhibition of Pathologic Immunoglobulin E in Food Allergy by EBF-2 and Active Compound Berberine Associated With Immunometabolism Regulation
Pathology, Microbiology & Immunology
INTRODUCTION: Food allergy is a significant public health problem with limited treatment options. As Food Allergy Herbal Formula 2 (FAHF-2) showed potential as a food allergy treatment, we further developed a purified version named EBF-2 and identified active compounds. We investigated the mechanisms of EBF-2 on IgE-mediated peanut (PN) allergy and its active compound, berberine, on IgE production. METHODS: IgE plasma cell line U266 cells were cultured with EBF-2 and FAHF-2, and their effects on IgE production were compared. EBF-2 was evaluated in a murine PN allergy model for its effect on PN-specific IgE production, number of IgE plasma cells, and PN anaphylaxis. Effects of berberine on IgE production, the expression of transcription factors, and mitochondrial glucose metabolism in U266 cells were evaluated. RESULTS: EBF-2 dose-dependently suppressed IgE production and was over 16 times more potent than FAHF-2 in IgE suppression in U266 cells. EBF-2 significantly suppressed PN-specific IgE production (70%, p<0.001) and the number of IgE-producing plasma cells in PN allergic mice, accompanied by 100% inhibition of PN-induced anaphylaxis and plasma histamine release (p<0.001) without affecting IgG1 or IgG2a production. Berberine markedly suppressed IgE production, which was associated with suppression of XBP1, BLIMP1, and STAT6 transcription factors and a reduced rate of mitochondrial oxidation in an IgE-producing plasma cell line. CONCLUSIONS: EBF-2 and its active compound berberine are potent IgE suppressors, associated with cellular regulation of immunometabolism on IgE plasma cells, and may be a potential therapy for IgE-mediated food allergy and other allergic disorders.
Yang, N., Maskey, A. R., Srivastava, K., Kim, M., Wang, Z., Musa, I., Shi, Y., Gong, Y., Fidan, O., Wang, J., Dunkin, D., Chung, D., Zhan, J., Miao, M., Sampson, H. A., & Li, X. (2023). Inhibition of Pathologic Immunoglobulin E in Food Allergy by EBF-2 and Active Compound Berberine Associated With Immunometabolism Regulation. https://doi.org/10.3389/fimmu.2023.1081121