Food Allergy Herbal Formula-2 Research Articles

Inhibition of pathologic immunoglobulin E in food allergy by EBF-2 and active compound berberine associated with immunometabolism regulation.

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. 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. 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. 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.

Inhibition of Pathologic Immunoglobulin E In Food Allergy by EBF2 and Active Compound Berberine Associated with Immunometabolism Regulation

Food allergy is a significant public health problem with limited treatment options. As Food Allergy Herbal Formula 2 (FAHF-2) showed potential for a food allergy treatment, we further developed a purified version named EBF2 and identified active compounds. We investigated the mechanisms of EBF2 on IgE-mediated peanut (PN) allergy and its active compound, berberine, on IgE production.

Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects.

Background: TNF-α has a major role in the pathogenesis of Crohn's disease (CD). In contrast, GM-CSF may be beneficial for its anti-inflammatory role in a subset of patients with CD with antibodies against GM-CSF as seen in prior trials of GM-CSF which resulted in clinical improvement in CD. We developed butanol purified Food Allergy Herbal Formula-2 (B-FAHF-2) by refining FAHF-2. FAHF-2 suppressed TNF-α production by human peripheral blood mononuclear cells (PBMCs) and colonic mucosa, and abrogated colitis in a murine model. We sought to examine the effect of B-FAHF-2 and the herbs that comprise it on TNF-α and GM-CSF production as a potential herbal therapy for the treatment of CD.Methods: B-FAHF-2 was examined using high pressure liquid chromatography (HPLC) and compared to the original formulation, FAHF-2. PBMCs from pediatric patients with CD were cultured with lipopolysaccharide and B-FAHF-2, individual herbs or medium alone. Colonic biopsy specimens were cultured with or without B-FAHF-2. TNF-α and GM-CSF were measured by enzyme-linked immunosorbent assay (ELISA). B-FAHF-2 efficacy was tested in vivo in the CD45Rbhi transfer model.Results: B-FAHF-2 had a similar HPLC fingerprint as FAHF-2 but decreased TNF-α production by PBMCs and colonic mucosa from pediatric CD subjects at 20% of the FAHF-2 dose. B-FAHF-2 increased GM-CSF production by PBMCs and colonic mucosa from pediatric CD subjects including those with antibodies to GM-CSF. Of B-FAHF-2's herbal constituents, only Huang Bai suppressed TNF-α and increased GM-CSF production. In the murine model, B-FAHF-2 treatment alleviated colitis.Conclusions: B-FAHF-2 decreased TNF-α production by PBMCs and colonic mucosa from pediatric subjects at a lower dose than FAHF-2. B-FAHF-2 also increased GM-CSF production by PBMCs independent of antibodies. B-FAHF-2 may have a benefit in CD patients.

Enhancing the Safety and Efficacy of Food Allergy Immunotherapy: a Review of Adjunctive Therapies.

Food allergy is a potentially life-threatening condition with no approved curative therapy. A number of food allergen immunotherapies are being investigated in phase II/III trials; however, these are limited in their ability to restore immune tolerance to food allergens and often result in high rates of allergic side effects, sometimes involving anaphylaxis, that may curtail their impact. A variety of adjunctive therapies have been developed in order to enhance the efficacy and/or improve the safety of food allergen immunotherapy through either shifting the immune response from a Th2 polarized response to a Th1 and regulatory T cell dominated response or by blocking downstream effects of the allergic inflammatory response by targeting IgE or mast cell mediators. Upstream therapies that shift towards a Th1/Treg response include toll-like receptor (TLR) 4 agonists (e.g., MPL and GLA), TLR9 agonists (CpG oligonucleotides), nanoparticles encapsulating peanut allergen (with and without adjuvants, such as CpG or rapamycin), Chinese herbal medicine (food allergy herbal formula (FAHF-2)), probiotics, and interferon-gamma. In contrast, anti-IgE therapies such as omalizumab, anti-histamines like ketotifen, and leukotriene receptor antagonists all target the downstream allergic response. Anti-IgE-based therapies appear to be furthest along with probiotics, Chinese herbal medicines, and TLR-4 agonists currently in early phase clinical trials. Meanwhile, nanoparticles represent an innovative delivery vehicle for immunotherapy that could improve both efficacy and decrease allergic side effects. Furthermore, other biologic therapies directed towards the allergic immune response are on the horizon. A number of factors will need to be evaluated in comparing these treatments, including ability to decrease allergic adverse events, safety of the adjunctive therapies themselves, effect on long-term sustained unresponsiveness, and cost. Further phenotyping of food allergy patients may be necessary to determine which ones respond best to each therapy. However, with so many promising adjunctive therapies, it appears likely that clinicians will have a variety of options to optimize the administration of food allergen immunotherapy. We provided a review of these methods, their influence on allergic adverse events, and utility in improving the immunomodulatory effects of food allergen immunotherapy.

Berberine as a chemical and pharmacokinetic marker of the butanol-extracted Food Allergy Herbal Formula-2

RationaleFood Allergy Herbal Formula-2 (FAHF-2) provided protection against peanut anaphylaxis in a murine model and induced beneficial immune-modulation in humans. Butanol-refined FAHF-2, B-FAHF-2, retained safety and efficacy in the peanut allergic murine model at only 1/5 of FAHF-2 dosage. One compound, berberine, was isolated and identified in vitro as a bioactive component present in FAHF-2 and B-FAHF-2. The aim of this study was to investigate berberine as a chemical and pharmacokinetic marker of B-FAHF-2. MethodsThe consistency of constituents between B-FAHF-2 and FAHF-2 was tested. Peanut allergic C3H/HeJ mice were orally administered with 1mg of berberine or B-FAHF-2 containing an equivalent amount of berberine, and the ability to protect against peanut anaphylaxis and pharmacokinetic parameters were determined. Human intestinal epithelial cells (Caco-2) were cultured with berberine with or without the nine individual herbal constituents in B-FAHF-2, and the absorbed berberine levels were determined. ResultsBerberine is one of the major components in B-FAHF-2 and FAHF-2 formula. In a peanut allergic mouse model, B-FAHF-2, but not berberine, protected mice from anaphylaxis reactions. Pharmacokinetic profiles showed that the Cmax of B-FAHF-2 fed mice was 289.30±185.40ng/mL; whereas berberine alone showed very low bioavailability with Cmax value of 35.13±47.90ng/mL. Caco-2 cells influx assay showed that 7 of 9 herbal constituents in B-FAHF-2 increased berberine absorption at rates ranging from 18 to 205%. ConclusionsB-FAHF-2 remarkably increased the bioavailability of berberine. Berberine can be used as chemical and pharmacokinetic marker of B-FAHF-2. Other herbal components in B-FAHF-2 may facilitate the absorption of berberine.

Anti-inflammatory Effects of Ganoderma lucidum Triterpenoid in Human Crohn's Disease Associated with Downregulation of NF-κB Signaling.

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Current medications have potentially serious side effects. Hence, there is increasing interest in alternative therapies. We previously demonstrated the anti-inflammatory effects of Food Allergy Herbal Formula-2 in vitro on peripheral blood mononuclear cells (PBMCs) and mucosa from CD subjects. Here, we investigated the anti-inflammatory effects of a bioactive compound isolated from Ganoderma lucidum (G. lucidum), a key herbal constituent of Food Allergy Herbal Formula-2, in CD in vitro. Triterpene ganoderic acid C1 (GAC1) was isolated from G. lucidum. Stimulated RAW 264.7 macrophages were treated with GAC1. Human PBMCs and colonic biopsies were obtained from children with CD and cultured with or without GAC1. TNF-α and other proinflammatory cytokine levels were measured in the culture supernatant. NF-κB signaling was investigated in PBMCs and colonic mucosa treated with GAC1 by In-Cell Western and Western blot analysis. GAC1 decreased TNF-α production by macrophages and PBMCs from CD subjects. GAC1 significantly decreased TNF-α, IFN-γ, and IL-17A production by inflamed colonic biopsies from CD subjects. These effects were due to downregulation of the NF-κB signaling pathway. GAC1 inhibited production of TNF-α and other proinflammatory cytokines by PBMCs and inflamed CD colonic mucosa due to blockage of NF-κB activation. GAC1 is a key beneficial constituent in G. lucidum and the Food Allergy Herbal Formula-2 in suppressing the inflammatory cytokines found in CD and warrants clinical investigation for the treatment of CD.

Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy

Food Allergy Herbal Formula-2 (FAHF-2) is a 9-herb formula based on traditional Chinese medicine that blocks peanut-induced anaphylaxis in a murine model. In phase I studies FAHF-2 was found to be safe and well tolerated. We sought to evaluate the safety and effectiveness of FAHF-2 as a treatment for food allergy. In this double-blind, randomized, placebo-controlled study 68 subjects aged 12 to 45 years with allergies to peanut, tree nut, sesame, fish, and/or shellfish, which were confirmed by baseline double-blind, placebo-controlled oral food challenges (DBPCFCs), received FAHF-2 (n = 46) or placebo (n = 22). After 6 months of therapy, subjects underwent DBPCFCs. For those who demonstrated increases in the eliciting dose, a repeat DBPCFC was performed 3 months after stopping therapy. Treatment was well tolerated, with no serious adverse events. By using intent-to-treat analysis, the placebo group had a higher eliciting dose and cumulative dose (P = .05) at the end-of-treatment DBPCFC. There was no difference in the requirement for epinephrine to treat reactions (P = .55). There were no significant differences in allergen-specific IgE and IgG4 levels, cytokine production by PBMCs, or basophil activation between the active and placebo groups. In vitro immunologic studies performed on subjects' baseline PBMCs incubated with FAHF-2 and food allergen produced significantly less IL-5, greater IL-10 levels, and increased numbers of regulatory T cells than untreated cells. Notably, 44% of subjects had poor drug adherence for at least one third of the study period. FAHF-2 is a safe herbal medication for subjects with food allergy and shows favorable in vitro immunomodulatory effects; however, efficacy for improving tolerance to food allergens is not demonstrated at the dose and duration used.

Epinephrine Use in Positive Oral Food Challenges Performed as a Screening Test for Food Allergy Therapy Trials

Previous studies report epinephrine use for positive oral food challenges (OFCs) to be 9-11% when generally performed to determine outgrowth of food allergies. Epinephrine use for positive OFCs performed as screening criteria for enrollment in therapeutic trials for food allergy has not been reported. The objective of this study was to assess the characteristics and treatment for positive OFCs performed for screening subjects for food therapeutic trials. Retrospective review of positive screening OFCs from 2 treatment trials, food allergy herbal formula-2 (n = 45) and milk oral immunotherapy (n = 29), conducted at the Icahn School of Medicine at Mount Sinai was performed. The most common initial symptom elicited was oral pruritus, reported for 81% (n = 60) of subjects. Overall, subjective gastrointestinal symptoms (oral pruritus, throat pruritus, nausea, abdominal pain) were most common (97.3% subjects), followed by cutaneous symptoms (48.7%). Of the 74 positive double-blind, placebo-controlled food challenge, 29 (39.2%) were treated with epinephrine; 2 of these subjects received 2 doses of epinephrine (6.9% of the reactions treated with epinephrine or 2.7% of all reactions). Biphasic reactions were infrequent, which occurred in 3 subjects (4%). Screening OFCs to confirm food allergies can be performed safely, but there was a higher rate of epinephrine use compared with OFCs used for assessing food allergy outgrowth. Therefore, personnel skilled and experienced in the recognition of early signs and symptoms of anaphylaxis who can promptly initiate treatment are required.

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

BackgroundCurrently, 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. ObjectiveTo determine which herbs and compounds in FAHF-2 and B-FAHF-2 suppress IgE production. MethodsThe 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. ResultsFAHF-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. ConclusionBerberine 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 RegistrationClinicaltrials.gov identifier NCT00602160.

In Vitro Immunomodulatory Effects of FAHF-2 (Food Allergy Herbal Formula-2) On PBMCs From Food Allergy Patients

FAHF-2 is highly effective in providing long-term protection against peanut-induced anaphylaxis in murine models, and appeared to be safe in human phase I clinical trials. Currently, a phase II clinical trial examining efficacy of FAHF-2 is on-going. The goal of this in vitro study was to investigate the immunological effects of FAHF-2 on PBMCs from food allergic patients enrolled in the current phase II trial.

Food allergy prevalence: new possibilities for therapy and prevention

Food allergy is an important clinical problem of increasing prevalence worldwide. Immunoglobulin E (IgE)-mediated allergic responses are the most widely recognized form of food allergy. The prevalence of food allergy is influenced by country, age, culture, and dietary habits. Strategies for the prevention of food allergy have been extensively studied. There is currently no standard treatment for food allergy and allergen-specific immunotherapy has been hindered by severe side effects in the past. A mutated recombinant major apple allergen is clinically hypoallergenic, which paves the way toward safer immunotherapy for the treatment of food-allergic patients.Traditional Chinese medicine (TCM) is one of the oldest medical practices in the world. A Chinese Food Allergy Herbal Formula-2 (FAHF-2) has been used as a therapy for food allergy patients. FAHF-2 was shown to be remarkably effective against food anaphylaxis in an animal model and in human clinical trial with the potential to be a long-lasting therapy.

Chinese Herbal Therapy for the Treatment of Food Allergy

Traditional Chinese medicine (TCM) has been widely used in China to treat various diseases for thousands of years. Given its reputed effectiveness, low cost, and favorable safety profile, TCM is attracting great interest in Western societies as a source of therapy for an array of illnesses, including allergies and asthma. Although food allergy has not been described in the TCM literature, a novel treatment for food allergy, named the food allergy herbal formula-2 (FAHF-2), was developed using TCM principles. Using a well-characterized murine model of peanut allergy, FAHF-2 has been shown to be highly effective in providing long-term protection against peanut-induced anaphylaxis, with a high safety margin. Phase 1 human trials have demonstrated the safety of FAHF-2 in food allergic individuals. Currently, a phase 2 trial examining efficacy of FAHF-2 is on-going. Other TCMs also show a potential for treating food allergies in preclinical studies.

Chemical and biological characterization of Food Allergy Herbal Formula 2 (FAHF-2) product consistency and potency

FAHF-2 has been shown to prevent peanut-induced anaphylaxis in a murine model. Phase I trials have demonstrated that FAHF-2 is a safe treatment for patients with food allergy. To complete the ongoing phase II study of safety and efficacy of FAHF-2, several batches of FAHF-2 were generated. The aim of this study was to analyze the chemical and biological consistency of different batches of FAHF-2 using our established methods. HPLC chromatogram data of each batch of FAHF-2 product were collected for analyzing product consistency. The bioactivities of 3 different batches of FAHF-2 (batch number1106, 0909 and 0202) were analyzed by culturingU266 (human B cell myeloma cell line), RBL-2H3 (mast cell line), and RAW 264.7 (mouse macrophage cell line) in the presence of 31, 62, 125, 250, and 500 μg/ml of FAHF-2. IgE production by U266, β-hexosaminidase release by RBL-2H3, and TNF-α production by RAW 264.7 cells were determined. Untreated cells were used as controls. Three biomarkers, berberine, jatrorrhizine, and ganoderic acid D, were used as indicators of FAHF-2 batch consistency. HPLC chromatogram data showed that batches of FAHF-2 had similar peak intensities of these three biomarkers. The in vitro assays showed that different batches of FAHF-2 all significantly inhibited IgE production by B cells, TNF-α production by macrophage cells, and degranulation by mast cells. IC50 values of 3 batches were comparable in the three bioactivity assays. This study shows that different batches of FAHF-2 used in clinical trials exhibited chemical consistency and biological potency in vitro.

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011

This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation.

Treatment of Asthma and Food Allergy With Herbal Interventions From Traditional Chinese Medicine

Prevalence of asthma and allergy has increased over the past 2-3 decades in Westernized countries. Despite increased understanding of the pathogenesis of asthma and allergic diseases, control of severe asthma is still difficult. Asthma is also associated with a high prevalence of anxiety, particularly in adolescents. There is no effective treatment for food allergy. Food allergy is often associated with severe and recalcitrant eczema. Novel approaches for treatment of asthma and food allergy and comorbid conditions are urgently needed. Traditional Chinese medicine, used in Asia for centuries, is beginning to play a role in Western healthcare. There is increasing scientific evidence supporting the use of traditional Chinese medicine for asthma treatment. Since 2005, several controlled clinical studies of "antiasthma" herbal remedies have been published. Among the herbal medicines, antiasthma herbal medicine intervention is the only antiasthma traditional Chinese medicine product that is a Food and Drug Administration investigational new drug that has entered clinical trials in the United States. Research into the effects and mechanisms of action of antiasthma herbal medicine intervention in animal models is actively being pursued. Research on traditional Chinese medicine herbal medicines for treating food allergy is rare. The herbal intervention Food Allergy Herbal Formula-2 is the only Food and Drug Administration botanical investigational new drug under investigation as a multiple food allergy therapy. This review article discusses promising traditional Chinese medicine interventions for asthma, food allergy, and comorbid conditions, and explores their possible mechanisms of action.

Oral tolerance induction protocols for treatment: an overview

Food allergy is a major health concern in industrialized countries, affecting approximately 3.9% of children. Peanut allergy is one of the most common forms of food allergy, with approximately 3 million Americans reporting allergy to peanuts or tree nuts, and the prevalence appears to be increasing. Peanut and tree nut allergy account for the vast majority of life-threatening or fatal allergic reactions to foods. In addition, peanut allergy is often life-long, with only 20% of children outgrowing their allergy. Current treatment options are limited to strict peanut avoidance and ready access to epinephrine. Challenges for patients and families with food allergy are considerable, and accidental ingestion is common. Anxiety impairs social functioning and quality of life in food-allergic individuals, who report poorer health-related quality of life than those with diabetes mellitus. These findings underscore the need for active treatment strategies. Animal and human studies have examined potential therapies for peanut allergy, including allergen-nonspecific and allergen-specific modalities; however, recent meta-analyses highlight the shortage of controlled studies in the field. TNX-901, a humanized monoclonal antibody that binds IgE and prevents its binding to the high-affinity IgE receptor on mast cells and basophils, was found to increase the threshold of peanut protein inducing symptoms in peanut-allergic individuals from less than one peanut (178 mg) to almost twelve peanuts (2805 mg). However, this effect was seen only at the highest dose tested, and the prohibitive cost of monoclonal antibody treatment may limit this approach. A combination of traditional Chinese herbal medications, food allergy herbal formula 2 (FAHF-2), has shown promise in eliminating anaphylaxis to peanut in murine and phase I studies. Allergen immunotherapy, an allergen-specific treatment, refers to the administration of increasing amounts of an allergen to individuals with IgE-mediated allergy in order to induce immunologic changes which diminish the allergic response to the substance on subsequent encounters. Traditional subcutaneous immunotherapy with aqueous peanut extract was attempted but had an unacceptably high rate of systemic reactions, despite favorable challenge outcomes. In pilot studies, our group has shown that open-label peanut oral immunotherapy (OIT) was relatively safe when performed in a supervised medical setting by trained personnel and was associated with clinical desensitization for the majority of subjects who completed more than eight months of treatment. We use the term desensitization to signify a change in threshold of ingested food antigen needed to cause allergic symptoms; this state is dependent on regular exposure to the allergen. In contrast, tolerance refers to the induction of long-term immunologic changes associated with the ability to ingest a food without symptoms and without ongoing therapy. In order to establish the safety and efficacy of peanut OIT as an allergen-specific therapy for peanut allergy, we conducted the first randomized, double-blind, placebo-controlled study of OIT in children with peanut allergy. Our goals were to evaluate the ability of peanut OIT to safely raise the threshold of ingested food antigen when compared with placebo and to perform immunologic studies to investigate the underlying mechanisms associated with clinical efficacy. The primary endpoint was to determine if, after one year of treatment, subjects receiving peanut OIT would be able to ingest a greater amount of peanut protein at food challenge than those receiving placebo.

Clinical safety of Food Allergy Herbal Formula-2 (FAHF-2) and inhibitory effect on basophils from patients with food allergy: Extended phase I study

Food allergy is a common and increasing health concern in westernized countries. No effective treatment is available, and accidental ingestion can be life-threatening. Food Allergy Herbal Formula-2 (FAHF-2) blocks peanut-induced anaphylaxis in a murine model of peanut-induced anaphylaxis. It was found to be safe and well tolerated in an acute phase I study of patients with food allergy. We sought to assess the safety of FAHF-2 in an extended phase I clinical trial and determine the potential effects on peripheral blood basophils from patients with food allergy. Patients in an open-label study received 3.3 g (6 tablets) of FAHF-2 three times a day for 6 months. Vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiographic data were acquired at baseline and at 2-month intervals. During the course of the study, basophil activation and basophil and eosinophil numbers were evaluated by using CCR3/CD63 staining and flow cytometry. Of 18 patients enrolled, 14 completed the study. No significant drug-associated differences in laboratory parameters, pulmonary function study results, or electrocardiographic findings before and after treatment were found. There was a significant reduction (P < .010) in basophil CD63 expression in response to ex vivo stimulation at month 6. There was also a trend toward a reduction in eosinophil and basophil numbers after treatment. FAHF-2 was safe and well tolerated and had an inhibitory effects on basophil numbers in an extended phase I clinical study. A controlled phase II study is warranted.

Bioactivities of Berberine, Palmatine, and Jatrorrhizine isolated from Food Allergy Herbal Formula 2 (FAHF-2)

RATIONALE: The herbal formula, FAHF-2, which contains 9 herbs, has been demonstrated to protect against peanut-induced anaphylaxis in a murine model of peanut-induced anaphylaxis. The aim of this study was to characterize the major components in FAHF-2 and investigate their biological activities in vitro.

Efficacy, safety and immunological actions of butanol‐extracted Food Allergy Herbal Formula‐2 on peanut anaphylaxis

Cite this as: K. Srivastava, N. Yang, Y. Chen, I. Lopez‐Exposito, Y. Song, J. Goldfarb, J. Zhan, H. Sampson and X‐M. Li, Clinical &amp; Experimental Allergy, 2011 (41) 582–591.SummaryBackground 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.Objectives 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.Conclusion and Clinical Relevance 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.

Food allergy herbal formula 2 protection against peanut anaphylactic reaction is via inhibition of mast cells and basophils

Mast cells and basophils are key effector cells of IgE-mediated anaphylactic reactions. The Chinese herbal formula, food allergy herbal formula 2 (FAHF-2), protects against peanut anaphylaxis in mice. However, the mechanisms underlying this effect are not fully elucidated. To investigate whether FAHF-2 inhibits mast cell/basophil numbers and IgE-mediated activation. Mice with peanut allergy (PNA mice) were treated with FAHF-2 intragastrically for 7 weeks and challenged intragastrically with peanut 1 day and 4 weeks posttreatment. Peripheral blood basophil numbers and peritoneal mast cell numbers and FcεRI expression were determined. Direct effects of FAHF-2 on the murine mast cell line MC/9, and effects of 4fractions and 3 compounds isolated from FAHF-2 on rat basophilic leukemia cells (RBL-2H3) and human skin mast cells degranulation and on the IgE-mediated spleen tyrosine kinase signaling pathway, were determined. Although all sham-treated PNA mice developed anaphylaxis, FAHF-2-treated PNA mice were protected against anaphylaxis after peanut challenge at 1 day and 4 weeks posttherapy. Reduction of peripheral blood basophils began after 1 week of treatment and continued for at least 4 weeks posttherapy. The number and FcεRI expression of peritoneal mast cells were also significantly decreased 4 weeks posttherapy. FAHF-2-treated MC/9 cells showed significantly reduced IgE-induced FcεRI expression, FcεRI γ mRNA subunit expression, proliferation, and histamine release on challenge. Fraction 2 from FAHF-2 inhibited RBL-2H3 cell and human mast cell degranulation. Three compounds from fraction 2-berberine, palmatine, and jatrorrhizine-inhibited RBL-2H3 cell degranulation via suppressing spleen tyrosine kinase phosphorylation. Food allergy herbal formula 2 reduction of basophils and mast cell numbers as well as suppression of IgE-mediated mast cell activation may contribute to FAHF-2's persistent protection against peanut anaphylaxis.