Efficacy, safety and immunological actions of butanol-extracted Food Allergy Herbal Formula-2 on peanut anaphylaxis.
BACKGROUND
Therapies for peanut allergy (PNA) are urgently needed. Food Allergy Herbal Formula-2 (FAHF-2) has profound therapeutic effects in a murine PNA model and is safe for food-allergic adults in clinical trials. However, the large FAHF-2 pill-load is not conducive to clinical studies in children. Thus, refining FAHF-2 to decrease pill-load is essential for the inclusion of children in clinical trials and to facilitate studying FAHF-2 as a clinically useful botanical drug.


OBJECTIVE
Testing long-term efficacy and safety of a butanol-purified extract of FAHF-2 (B-FAHF-2) in a murine model of PNA, and to explore its immunological mechanisms of action.


METHODS
FAHF-2 was purified by butanol extraction. C3H/HeJ mice with established PNA received the first course of B-FAHF-2 at 6 mg, twice daily for 7 weeks (PNA/B-FAHF-2) or water (PNA/sham) and were then challenged immediately after completing the treatment and six more times every 1-2 months post-treatment up to week 50. Mice then received a second course of B-FAHF-2 treatment at week 52 and were challenged at week 65. In vivo and in vitro immunological effects on T, B and mast cells were also determined.


RESULTS
Butanol purification reduced the volume of the effective dose ∼5-fold. All PNA/B-FAHF-2 mice were completely protected from PN anaphylaxis until the fifth challenge after the first course of treatment, as compared with PNA/sham mice. Partial protection persisted up to 50 weeks. A second treatment course restored complete protection. B-FAHF-2 significantly suppressed Th2 cytokine, IgE and histamine levels in vivo, and showed direct inhibition of Th2, IgE-producing B cells and mast cell activation in vitro. B-FAHF-2 had a high margin of safety.


CONCLUSIONS
B-FAHF-2 produced long-lasting protection against PN anaphylaxis for approximately half of the murine life span without side-effects. B-FAHF-2 exhibited direct effects on multiple food allergy effector cells.
Department of Pediatrics Jaffe Food Allergy Institute Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
K
K
Srivastava
N
N
Yang
Y
Y
Chen
I
I
Lopez-Exposito
Y
Y
Song
J
J
Goldfarb
J
J
Zhan
H
H
Sampson
X-M
XM
Li
D000707:Anaphylaxis / Q000517:prevention & control*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D000440:Butanols / Q000737:chemistry; D005591:Chemical Fractionation / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D051379:Mice; D021183:Peanut Hypersensitivity / Q000517:prevention & control*; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000440:Butanols; D016207:Cytokines; C497376:Food Allergy Herbal Formula-2; D007074:Immunoglobulin G; D010936:Plant Extracts; D007073:Immunoglobulin E