title: Berberine and limonin suppress IgE production by human B cells and peripheral blood mononuclear cells from food-allergic patients.
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Clinicaltrials.gov identifier NCT00602160.
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Julie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Changda
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Biological Engineering, Utah State University, Logan, Utah.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biological Engineering, Utah State University, Logan, Utah.
authors.forename: Jiachen
authors.initials: J
authors.lastname: Zi
authors.affiliation: Department of Biological Engineering, Utah State University, Logan, Utah.
authors.forename: Jixun
authors.initials: J
authors.lastname: Zhan
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Madhan
authors.initials: M
authors.lastname: Masilamani
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Amanda
authors.initials: A
authors.lastname: Cox
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Anna
authors.initials: A
authors.lastname: Nowak-Wegrzyn
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Hugh
authors.initials: H
authors.lastname: Sampson
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: xiu-min.li@mssm.edu.
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000293:Adolescent; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D001599:Berberine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002648:Child; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D020672:I-kappa B Proteins / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D036701:Limonins / Q000494:pharmacology*; D008297:Male; D021183:Peanut Hypersensitivity / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000276:immunology; D020825:T-Box Domain Proteins / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: C418974:FOXP3 protein, human; C497376:Food Allergy Herbal Formula-2; D051858:Forkhead Transcription Factors; D020672:I-kappa B Proteins; C508599:IL5 protein, human; D015848:Interleukin-5; D036701:Limonins; D010936:Plant Extracts; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D001599:Berberine; D016753:Interleukin-10; D007073:Immunoglobulin E; D007371:Interferon-gamma; C001546:limonin