Inhibition of Pathologic Immunoglobulin E in Food Allergy by EBF-2 and Active Compound Berberine Associated With Immunometabolism Regulation

Authors

• Nan Yang, General Nutraceutical Technology, Elmsford, NY, United States.Follow
• Anish R. Maskey, Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States.Follow
• Kamal Srivastava, General Nutraceutical Technology, Elmsford, NY, United States.Follow
• Monica Kim, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.Follow
• Zixi Wang, Department of Allergy, Peking Union Medical College Hospital, Beijing, China.
• Ibrahim Musa, Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States.
• Yanmei Shi, Academy of Chinese Medicine Sciences, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China.
• Yixuan Gong, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
• Ozkan Fidan, Department of Biological Engineering, Utah State University, Logan, UT, United States.
• Julie Wang, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
• David Dunkin, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
• Danna Chung, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
• Jixun Zhan, Department of Biological Engineering, Utah State University, Logan, UT, United States.
• Mingsan Miao, Academy of Chinese Medicine Sciences, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China.
• Hugh A. Sampson, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
• Xiu-Min Li, Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States.Follow

Author Type(s)

Faculty

DOI

10.3389/fimmu.2023.1081121

Journal Title

Frontiers in Immunology

First Page

1081121

Document Type

Article

Publication Date

1-1-2023

Department

Pathology, Microbiology and Immunology

Keywords

IgE, anaphylactic allergic reaction, berberine, food allergy, metabolism

Disciplines

Medicine and Health Sciences

Abstract

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.

Recommended Citation

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. Frontiers in Immunology, 14, 1081121. https://doi.org/10.3389/fimmu.2023.1081121