Berberine and limonin suppress IgE production by human B cells and peripheral blood mononuclear cells from food-allergic patients

Ann Allergy Asthma Immunol. 2014 Nov;113(5):556-564.e4. doi: 10.1016/j.anai.2014.07.021. Epub 2014 Aug 22.


Background: Currently, there is no satisfactory treatment for IgE-mediated food allergy. Food Allergy Herbal Formula 2 (FAHF-2) and butanol-purified FAHF-2 (B-FAHF-2) have been shown to protect against peanut-induced anaphylaxis and inhibit IgE synthesis in a murine model.

Objective: To determine which herbs and compounds in FAHF-2 and B-FAHF-2 suppress IgE production.

Methods: The effect of FAHF-2 and B-FAHF-2 on IgE production was determined using a human B-cell line (U266). Individual compounds were isolated and identified using column chromatography, liquid chromatographic mass spectrometry, and nuclear magnetic resonance techniques. The potency of compounds on IgE suppression were investigated using U266 cells and verified using human peripheral blood mononuclear cells (n = 25) from peanut-allergic patients. Epsilon germline transcript expression was determined. Phosphorylated IκBα level was analyzed using the In-Cell Western assay. The mRNA expression of signal transducer and activator of transcription-3, T-box transcription factor TBX21, interferon-γ, forkhead box P3, GATA-binding protein 3, interleukin-10, and interleukin-5 also were analyzed using real-time polymerase chain reaction.

Results: FAHF-2 and B-FAHF-2 inhibited IgE production by U266 cells. B-FAHF-2 was 9 times more effective than FAHF-2. Two compounds that inhibited IgE production were isolated from Philodendron chinensis and identified as berberine and limonin. Berberine was more potent and inhibited IgE production by peripheral blood mononuclear cells by 80% at 0.62 μg/mL. Berberine significantly inhibited ε-germline transcript expression by peripheral blood mononuclear cells. Phosphorylated IκBα level was significantly suppressed and mRNA expressions of T-box transcription factor TBX21 and signal transducer and activator of transcription-3 were significantly increased by berberine.

Conclusion: Berberine and limonin mediated IgE suppression. The mechanism by which berberine modulates ε-germline transcript expression might be through regulating the phosphorylated IκBα level and the expressions of signal transducer and activator of transcription-3 and T-box transcription factor TBX21.

Trial registration: identifier NCT00602160.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Berberine / pharmacology*
  • Cell Line, Tumor
  • Child
  • Female
  • Forkhead Transcription Factors / immunology
  • Humans
  • I-kappa B Proteins / immunology
  • Immunoglobulin E / biosynthesis*
  • Immunoglobulin E / immunology
  • Interferon-gamma / immunology
  • Interleukin-10 / immunology
  • Interleukin-5 / immunology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Limonins / pharmacology*
  • Male
  • Peanut Hypersensitivity / blood*
  • Peanut Hypersensitivity / drug therapy*
  • Peanut Hypersensitivity / immunology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Real-Time Polymerase Chain Reaction
  • STAT3 Transcription Factor / immunology
  • T-Box Domain Proteins / immunology


  • FOXP3 protein, human
  • Food Allergy Herbal Formula-2
  • Forkhead Transcription Factors
  • I-kappa B Proteins
  • IL5 protein, human
  • Interleukin-5
  • Limonins
  • Plant Extracts
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Berberine
  • Interleukin-10
  • Immunoglobulin E
  • Interferon-gamma
  • limonin

Associated data