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Objective To summarize the recent evidence of traditional Chinese medicine (TCM) for food allergy and eczema. Data Sources Published literature from PubMed database and abstract conference presentations. Study Selections Studies relevant to TCM for food allergy and eczema were included. Results TCM is the main component of complementary and alternative medicine in the United States. Food Allergy Herbal Formula 2 (FAHF-2) (derived from the classical formula Wu Mei Wan) prevented systemic anaphylaxis in murine models and was found to have safety and preliminary immunomodulatory effects on T cells and basophils. The phase II trial of combined TCM with oral immunotherapy and omalizumab for multiple food allergy is ongoing. Retrospective practice-based evidence study revealed that comprehensive TCM therapy effectively prevented frequent and severe food anaphylaxis triggered by skin contact or protein inhalation. The traditional Japanese herbal medicine Kakkonto suppressed allergic diarrhea and decreased mast cells in intestinal mucosa in a murine model. The active compounds from TCM were found to have potent inhibition of immunoglobulin (Ig) E, mast cell activation, and proinflammatory cytokine or signaling pathway (tumor necrosis factor alpha, interleukin 8, NF-κB) suggesting value for both IgE and non–IgE-mediated food allergy. Triple TCM therapy including ingestion, bath, and cream markedly improved skin lesion, itching, and sleep loss in patients with corticosteroid dependent, recalcitrant, or topical steroid withdrawal. Xiao Feng San and Japanese and Korean formulas were found to have effectiveness in eczema. Furthermore, acupuncture reduced wheal size, skin itching, and basophil activation in atopic dermatitis. Moreover, TCM is generally safe. Conclusion TCM has potential as safe and effective therapy for food allergy and eczema. Further research is needed for botanical drug development and to further define the mechanisms of actions. Trial Registration FAHF-2: https://ichgcp.net/clinical-trials-registry/NCT00602160 ; ethyl acetate and butanol purified FAHF-2: https://clinicaltrials.gov/ct2/show/NCT02879006 .

Background Complementary and alternative medicines (CAM), such as herbal remedies, are widely used by patients with chronic diseases, such as asthma. However, it is unclear whether use of the herbal remedies is associated with decreased adherence to inhaled corticosteroids (ICSs), a key component of asthma management. Objective To examine the association among use of herbal remedies, adherence to prescribed ICSs, and medication and disease beliefs. Methods We surveyed 326 adults with persistent asthma who received care at 2 inner-city outpatient clinics. Patients were asked about CAM use (teas, herbs, and rubs) for the treatment of asthma in the prior 6 months. Medication adherence was assessed using the Medication Adherence Report Scale, a validated self-report measure. Univariate and multiple regression analyses were used to assess the relationship among herbal remedy use, adherence to ICSs, and medication and disease beliefs. Results Overall, 25.4% (95% confidence interval, 20%–30%) of patients reported herbal remedy use. Univariate analyses showed that herbal remedy use was associated with decreased ICS adherence and increased asthma morbidity. In multivariable analysis, herbal remedy use was associated with lower ICS adherence (odds ratio, 0.4; 95% confidence interval, 0.2–0.8) after adjusting for confounders. Herbal remedy users were also more likely to worry about the adverse effects of ICSs ( P = .01). Conclusions The use of herbal remedies was associated with lower adherence to ICSs and worse outcomes among inner-city asthmatic patients. Medication beliefs, such as worry about ICS adverse effects, may in part mediate this relationship. Physicians should routinely ask patients with asthma about CAM use, especially those whose asthma is poorly controlled.

Mucous hypersecretion increases asthma morbidity and mortality. Tumor necrosis factor a (TNF-a) levels are elevated in bronchoalveolar fluid, sputum, and monocyte membranes in some patients with asthma. Anti-TNF-a decreased asthma exacerbations and improved forced expiratory volume in 1 second in these patients. Whether anti-TNF-a reduces mucous cell metaplasia or hyperplasia has not been evaluated.To investigate the role of anti-TNF-alpha in mucous hypersecretion.BALB/c mice sensitized intraperitoneally and challenged intratracheally with ovalbumin were treated with 250 microg of anti-TNF-alpha before ovalbumin sensitization and challenge or before only ovalbumin challenge. Control groups were sham treated. The tumor necrosis factor receptor (TNFR) mice (TNFR-/- and TNFR+/+) were identically sensitized and challenged. Seventy-two hours after the final challenge, the airway pressure time index (APTI), which measures airway hyperresponsiveness, was recorded. Mucous cell metaplasia was accessed by quantitative polymerase chain reaction for MUC-5AC (the epithelial cell mucous-inducing gene) and the percentage of periodic acid-Schiff (PAS) staining of bronchial epithelial cells. A human airway cell line (constitutively expressing MUC-5AC) was pretreated with a NF-kappaB inhibitor before TNF-alpha culture.The mean (SE) fold change of MUC-5AC expression (compared with naive controls), the percentage of PAS-positive bronchiole epithelial cells, and the APTI decreased in BALB/c mice treated with anti-TNF-alpha before sensitization and challenge (4.9 [1.14], P = .007; 28.9% [6.8%], P.001; and 545.8 [104.5] cm H2O/s, P.001, respectively) and before challenge alone (9.3 [1.8], P = .03; 43.6% [10.7%], P = .009; and 896.8 [81.23] cm H2O/s, P = .06, respectively) compared with sham-treated mice (20.9 [3.9], 82.4% [1.8%], and 1,055 [30.6] cm H20/s, respectively). MUC-5AC expression decreased in ovalbumin sensitized or challenged TNFR-/- (2.41 [0.4]) compared with ovalbumin sensitized or challenged TNFR+/+ mice (18.4 [2.5], P.001). TNF-alpha-induced MUC-5AC expression in human airway culture significantly decreased with pretreatment of a NF-kappaB inhibitor.Anti-TNF-alpha treatment reduces airway mucous cell metaplasia in a mouse model of asthma, which may in part underlie its beneficial effect as asthma therapy.

Objective To discuss the potential use of the Chinese herbal formula MSSM-002 in treating asthma based on its effects on a murine model of allergic asthma, immunoregulatory actions on T H 2 cells in vitro, and the means of standardization for herbal formula quality control. Data Sources Information presented at the 2002 American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting International Symposium on Complementary Alternative Medicine in San Antonio, TX. Study Selection All presentations from the ACAAI meeting that discussed MSSM-002 were considered for this review. Results The Chinese herbal formula MSSM-002 suppressed airway hyperreactivity and eosinophilic inflammation in a murine model of allergic asthma. These effects were comparable to dexamethasone but were not accompanied by the suppression of T H 1 responses seen with dexamethasone. In vitro studies demonstrated that MSSM-002 significantly decreased antigen-induced T H 2 cytokine secretion by murine T H 2 polarized splenocytes and human mucosal T H 2 cell lines, which in contrast to dexamethasone did not cause apoptosis and was not cytotoxic but was associated with decreased GATA-3 expression. Chromatographic fingerprints of MSSM-002 and evaluation of in vivo actions showed that the quality of several batches of MSSM-002 was consistent. Conclusion MSSM-002 has a therapeutic effect on allergic asthma and immunoregulatory actions on established T H 2 cells and may prove to be of potential clinical benefit to asthma patients.

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 e-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 e-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 Clinicaltrials.gov identifier NCT00602160.

Background Neutrophil-predominant asthma is less responsive to steroids and associated with poorer disease control. The effects of Antiasthma Simplified Herbal Medicine Intervention (ASHMI), a traditional Chinese medicine formula reported to be efficacious in asthmatic patients and murine asthma models, on neutrophil predominant asthma are unknown. Objective To determine the effects of standard ASHMI and refined formula ASHMI (ASHMI II ) in a neutrophil-predominant murine model of ragweed (RW) asthma and explore underlying mechanisms. Methods BALB/c mice were systemically sensitized, intranasally challenged with RW extract, and orally treated with ASHMI, ASHMI II , or vehicle (water). In a separate experiment, some RW sensitized mice were treated with dexamethasone before challenge. After RW challenge, airway hyperreactivity (AHR), total and differential bronchoalveolar lavage fluid leukocyte counts, lung histologic features, and bronchoalveolar lavage fluid cytokine and chemokine levels were assessed. RW stimulation of the murine macrophage cell line RAW264.7 was used to determine effects of ASHMI active compound ganoderic acid C1 (GAC1) on tumor necrosis factor α (TNF-α) production and regulation of phosphorylated IκB and histone deacetylase 2 (HDAC2) levels. Results ASHMI and ASHMI II markedly reduced AHR, mucous production, neutrophilic inflammation, and TNF-α, interleukin 8, and interleukin 17 levels and decreased eosinophilic inflammation and T H 2 responses in vivo ( P Conclusion ASHMI treatment was efficacious in a murine model of neutrophil-predominant asthma via modulation of innate chemokines, T H 2 responses, nuclear factor–κB, and HDAC2. ASHMI, and/or its constituent GAC1, may be a valuable option for treating neutrophil-predominant asthma.

Background Food Allergy Herbal Formula-2 (FAHF-2) prevents anaphylaxis in a murine model of peanut allergy. Multiple food allergies (MFA) are common and associated with a higher risk of anaphylaxis. No well-characterized murine model of sensitization to multiple food allergens exists, and no satisfactory therapy for MFA is currently available. Objective To determine the effect of FAHF-2 in a murine model of MFA. Methods C3H/HeJ mice were orally sensitized to peanut, codfish, and egg concurrently. Oral FAHF-2 treatment commenced 1 day after completing sensitization and continued daily for 7 weeks. Mice were subsequently orally challenged with each allergen. Results Antibodies in sera from mice simultaneously sensitized with peanut, codfish, and egg recognized major allergens of all 3 foods, demonstrating sensitization to multiple unrelated food allergens (MFA mice). Sham-treated MFA mice exhibited anaphylactic symptoms accompanied by elevation of plasma histamine and hypothermia. In contrast, FAHF-2–treated MFA mice showed no anaphylactic symptoms, normal body temperature, and histamine levels after challenge with each allergen. Protection was accompanied by reduction in allergen-specific immunoglobulin E levels. Allergen-stimulated Th2 cytokine interleukin-4 and interleukin-13 production levels decreased, whereas the Th1 cytokine interferon-γ levels were elevated in cultured splenocytes and mesenteric lymph node cells in FAHF-2–treated mice. Conclusion We established the first murine model of MFA. FAHF-2 prevents peanut, egg, and fish-induced anaphylactic reactions in this model, suggesting that FAHF-2 may have potential for treating human MFA.

Background Food allergy is a common and serious health problem. A new herbal product, called food allergy herbal formula 2 (FAHF-2), has been demonstrated to have a high safety profile and potent long-term efficacy in a murine model of peanut-induced anaphylaxis. Objective To evaluate the safety and tolerability of FAHF-2 in patients with food allergy. Methods In this randomized, double-blinded, placebo-controlled, dose escalation, phase 1 trial, patients received 1 of 3 doses of FAHF-2 or placebo: 2.2 g (4 tablets), 3.3 g (6 tablets), or 6.6 g (12 tablets) 3 times a day for 7 days. Four active and 2 placebo patients were treated at each dose level. Vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiogram data were monitored. Immunomodulatory studies were also performed. Results Nineteen food allergic participants were included in the study. Two patients (1 in the FAHF-2 group and 1 in the placebo group) reported mild gastrointestinal symptoms. One patient withdrew from the study because of an allergic reaction that was unlikely related to the study medication. No significant differences were found in vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiogram data obtained before and after treatment visits. Significantly decreased interleukin (IL) 5 levels were found in the active treatment group after 7 days. In vitro studies of peripheral blood mononuclear cells cultured with FAHF-2 also demonstrated a significant decrease in IL-5 and an increase in culture supernatant interferon γ and IL-10 levels. Conclusions FAHF-2 appeared to be safe and well tolerated in patients with food allergy. Trial Registration clinicaltrials.gov Identifier: NCT00602160 .

Background Although asthma is typically characterized as a childhood disease, it can develop later in life. Older asthmatic patients may be at increased risk for corticosteroid adverse effects. We developed a novel traditional Chinese medicine to treat asthma called antiasthma simplified herbal medicine intervention (ASHMI). Herbal products may offer safer adjunctive treatment for older asthmatic patients. Objective To investigate the effects of ASHMI on characteristics of allergic asthma in an aged mouse model of asthma. Methods BALB/c mice (6 weeks old [young] and 6, 12, and 18 months old [aged]) received ASHMI treatment before and during intraperitoneal ovalbumin sensitization and intratracheal challenges. The control groups were untreated, age-matched, ovalbumin-sensitized and ovalbumin-challenged mice (ovalbumin mice) and naive mice. After the final antigen challenge, airway pressure (defined as the time-integrated change in peak airway pressure) after acetylcholine provocation was measured, representing airway hyperresponsiveness, and bronchoalveolar lavage fluid, sera, lung tissues for histologic analysis, messenger RNA, and collagen were collected. Results Mean time-integrated change in peak airway pressure values in 6-week-old and 6-, 12-, and 18-month-old ASHMI ovalbumin mice were significantly reduced compared with those of age-matched, nontreated ovalbumin mice. Bronchoalveolar lavage fluid eosinophil numbers were significantly lower in all ASHMI ovalbumin mice. Treatment with ASHMI of young and aged ovalbumin mice resulted in significantly decreased lung inflammation, detected via hematoxylin-eosin staining; airway mucous cell metaplasia, determined by means of periodic acid–Schiff staining; and messenger RNA copy numbers of the mucin gene MUC5AC. Levels of ovalbumin specific IgE and the T H 2 cytokines interleukin 4 (IL-4), IL-5, and IL-13 in lung and splenocyte cultures were reduced. Interferon gamma secretion was increased. Treatment with ASHMI reduced collagen production. Conclusion Treatment with ASHMI reduces several features of asthma in aged antigen-sensitized and antigen-challenged mice.