Anti-asthma Herbal Medicine Intervention Research Articles

Formononetin isolated from Sophorae flavescentis inhibits B cell-IgE production by regulating ER-stress transcription factor XBP-1.

IgE plays an important pathologic role in most, if not all, allergic conditions. We previously showed that ASHMI (anti-asthma herbal medicine intervention) suppressed IgE production in murine models of asthma and in asthma subjects. However, the active compounds in ASHMI responsible for the IgE suppression are still unknown. We sought to identify the compound(s) in ASHMI that are responsible for IgE inhibition as well as investigate the mechanisms by which the identified compound(s) decreases IgE production. The compounds in Sophorae Flavescentis were separated using Column chromatography and preparative-HPLC. The separated compounds were identified using LC-MS and 1H-NMR. U266 cells, an IgE-producing plasma cell line, were cultured with various concentrations of identified compounds. The levels of IgE production by the U266 cell were measured by ELISA. Trypan blue exclusion was used to determine the cell viability. The gene expression of XBP-1 and IgE-heavy chain was determined by RT-PCR. A single compound identified as formononetin was isolated from Sophorae Flavescentis. Formononetin significantly and dose dependently decreased the IgE production in U266 cells across a concentration range of 2-20 µg/ml (p < 0.05-0.001 vs. untreated cells) with an IC50 value of 3.43 μg/ml. There was no cytotoxicity at any tested concentration. Formononetin significantly decreased XBP-1, and IgE-heavy chain gene expression compared with untreated cells (p < 0.001). Formononetin decreased IgE production in human B cell line U266 cells in a dose-dependent fashion through the regulation of XBP-1 ER transcription. Formononetin may be a potential therapy for allergic asthma and other IgE-mediated diseases.

Traditional Chinese Herbal Medicine and Corticosteroids in Asthma: A short review.

Asthma is a prevalent chronic inflammatory disease that has gold standard treatment with corticosteroids, but these are associated with important long-term side effects. On this basis, Traditional Chinese Medicine contributes with therapeutic techniques such as the herbal Anti-Asthma Herbal Medicine Intervention (ASHMI). In this context, this study aims to evaluate the effectiveness of treatment with ASHMI compared to conventional therapy, considering the need for new therapeutic approaches. An integrative review was performed, according to the PRISMA methodology. Articles published between 2011 and 2021 that related Herbal Medicines of Traditional Chinese Medicine, asthma and corticosteroids were examined. The searches took place in October and November 2021 in the Scopus, PubMed, Web of Science, Google Scholar, and Scielo databases. The selection comprised steps such as: search, pre-selection and inclusion of articles. The results of the herbal medicine and its isolated components were demonstrated, with three studies being clinical trials with humans and four pre-clinical studies. From the results, the efficacy of the herbal medicine and its components compared to corticosteroids were evaluated. It was reported that ASHMI, unlike corticosteroids, does not suppress the hypothalamic-pituitary-adrenal axis and the immune system, having mild adverse effects

Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma.

PurposeIsoliquiritigenin (ILQ), an important component of Anti-Asthma Herbal Medicine Intervention (ASHMI), had shown potent anti-asthma effect in vitro in our previous study. However, poor solubility and low bioavailability hindered in vivo application to treat asthma. This study was to develop a novel ILQ loaded self-nanoemulsifying drug delivery system (ILQ-SMEDDS) with enhanced bioavailability.MethodsThe optimized SMEDDS formulation was composed of ethyl oleate (oil phase), Tween 80 (surfactant) and PEG400 (co-surfactant) at a mass ratio of 3:6:1. The physiochemical properties of ILQ-SMEDDS, including drug content, globule size, zeta potential, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, were characterized. And the in vitro release profile, in situ intestinal absorption, in vivo pharmacokinetic parameters and the anti-asthma effect of ILQ suspension and ILQ-SMEDDS were evaluated.ResultsThe ILQ-SMEDDS had an average globule size of 20.63 ± 1.95 nm with a polydispersity index (PDI) of 0.11 ± 0.03, and its zeta potential was −12.64 ± 2.12 mV. The cumulative release rate of ILQ from ILQ-SMEDDS to the simulated gastrointestinal tract was significantly higher than that of free ILQ suspension. And area under curve with ILQ-SMEDDS was found to be 3.95 times higher than that of ILQ suspension indicating improved bioavailability by SMEDDS. Although ILQ-SMEDDS showed a slight less effective inhibitory effect on eotaxin-1 in human lung fibroblast (HFL-1) cells than free ILQ, in an ovalbumin-induced asthma model, ILQ-SMEDDS exhibited more efficacy than ILQ suspension in improving asthma-associated inflammation, including eosinophil production, ovalbumin-specific immunoglobulin E (OVA-sIgE), interleukin 4 (IL 4), interleukin 5 (IL 5) and interferon-γ (IFN-γ). Even the low dose of ILQ-SMEDDS group (10 mg/kg) showed better anti-asthma effect than that of the ILQ suspension group (20 mg/kg).ConclusionCompared with ILQ suspension, ILQ-SMEDDS showed significantly improved bioavailability and anti-asthma effect, revealing its potential as a favorable pharmaceutical agent for treating asthma.

Systems pharmacology uncovers the mechanisms of anti-asthma herbal medicine intervention (ASHMI) for the prevention of asthma

Asthma is a common chronic inflammatory airway disorder associated with considerable morbidity, mortality and increased health care costs worldwide. Traditional Chinese medicine (TCM) as a functional food characterized by multi-compound and multi-target have been proven to be effective in treating asthma based on a holistic way. However, the potential molecular or systems mechanism of TCM to anti-asthma has not yet been fully elucidated. A systems pharmacology-based method combining the ADME evaluation, herb feature mapping, drug target fishing, network pharmacology, as well as pathway analysis is developed to comprehensively elucidate the potential therapeutic mechanism of asthma, exemplified by the anti-asthma herbal medicine intervention (ASHMI). Our study not only provides a comprehensive thinking for better understanding the complex action mechanism of ASHMI on asthma from a system level, but also proposed a rational novel way to facilitate the treatment of asthma.

Glycyrrhiza uralensis flavonoids inhibit brain microglial cell TNF-α secretion, p-IκB expression, and increase brain-derived neurotropic factor (BDNF) secretion

ObjectiveAsthma sufferers exhibit high prevalence of anxiety/depression. Elevated tumor-necrosis factor-alpha (TNF-α) levels in peripheral system and central nervous system (CNS) are associated with anxiety/depression, whereas brain-derived neurotropic factor (BDNF) has anti-depressant effects. An anti-asthma herbal medicine intervention ASHMI inhibits peripheral TNF-α secretion in an animal model of asthma. We hypothesize that ASHMI and its compounds may have modulatory effects on CNS TNF-α and BDNF production. We sought to determine the effect of ASHMI and individual herb constituents on brain microglial cell TNF-α production, and identify the active compounds that suppress TNF-α and increase BDNF. MethodsBV-2 mouse microglial cells were pre-treated with ASHMI or extracts of Ganoderma lucidum (G. lucidum), Sophora flavescens Ait (S. flavescens), and Glycyrrhiza uralensis Fischer (G. uralensis), the herbal constituents in ASHMI, or individual compounds isolated from G. uralensis at different concentrations and then stimulated with LPS. TNF-α levels in culture supernatants were measured by ELISA. The effect of active compounds on NFκB signaling pathway and on BDNF production were determined by western blotting and ELISA, respectively. ResultsASHMI produced dose-dependent inhibition of TNF-α secretion by cultured-mouse microglia BV2 cells. Of the three herb extracts in ASHMI, only G. uralensis significantly and dose-dependently inhibited TNF-α production. Among the 5 flavonoids isolated from G. uralensis, isoliquiritigenin was the most effective. Isoliquiritigenin suppression of TNF-α production was associated with attenuation of p-NF-κB expression, and was accompanied by increased BDNF secretion. ConclusionASHMI and its effective flavonoid, isoliquiritigenin, inhibited TNF-α production by LPS stimulated microglial cells and elevated BDNF levels, which may prove to have anti-CNS inflammatory and anti-anxiety effects.

The Sophora flavescens flavonoid compound trifolirhizin inhibits acetylcholine induced airway smooth muscle contraction.

Asthma is a serious health problem worldwide, particularly in industrialized countries. Despite a better understanding of the pathophysiology of asthma, there are still considerable gaps in knowledge as well as a need for classes of drugs. ASHMI™ (Anti-asthma Herbal Medicine Intervention) is an aqueous extract of Ganoderma lucidum (Fr.) P. Karst (Ling Zhi), Sophora flavescens Aiton (Ku Shen) and Glycyrrhiza uralensis Fisch. ex DC (Gan Cao). It prevents allergic asthma airway hyper-reactivity in mice and inhibits acetylcholine (ACh) induced airway smooth muscle (ASM) contraction in tracheal rings from allergic asthmatic mice. The purpose of this research was to identify individual herb(s) and their active compound(s) that inhibit ASM contraction. It was found that S. flavescens, but not G. lucidum or G. uralensis aqueous extracts, inhibited ASM contraction in tracheal rings from asthmatic mice. Bioassay-guided isolation and identification of flavonoid fractions/compound(s) via methylene chloride extraction, preparative HPLC fractionation, and LC-MS and NMR spectroscopic analyses showed that trifolirhizin is an active constituent that inhibits acetylcholine mediated ASM contraction or directly relaxes pre-contracted ASM independent of β2-adrenoceptors.

Constituents of the anti-asthma herbal formula ASHMI™ synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro

Anti-asthma herbal medicine intervention (ASHMI(TM)), a combination of three traditional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMI(TM) exhibited synergy. Effects of ASHMI and its components aqueous extracts of Lingzhi (Ganoderma lucidum), Kushen (Sophora flavescens) and Gancao (Glycyrrhiza uralensis), on Th2 cytokine secretion by murine memory Th2 cells (D10.G4.1) and eotaxin-1 secretion by human lung fibroblast (HLF-1) cells were determined by measuring levels in culture supernatants by enzyme-linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters. Individual Lingzhi, Kushen and Gancao extracts and ASHMI (the combination of individual extracts) inhibited production of interleukin (IL)-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration (IC25) values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50 values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-1. The interaction indices at IC50 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC50 values. All interaction indices were below 1 which indicated synergy. By comparing the interaction index values, we find that constituents in ASHMI(TM) synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.

Glycyrrhiza uralensis Flavonoids Present in Anti‐Asthma Formula, ASHMITM, Inhibit Memory Th2 Responses in Vitro and in Vivo

Allergic asthma is associated with Th2-mediated inflammation. Several flavonoids were isolated from Glycyrrhiza uralensis, one of the herbs in the anti-asthma herbal medicine intervention. The aim of this investigation was to determine whether Glycyrrhiza uralensis flavonoids have inhibitory effects on memory Th2 responses in vitro and antigen-induced Th2 inflammation in vivo. The effects of three Glycyrrhiza uralensis flavonoids on effector memory Th2 cells, D10.G4.1 (D10 cells), were determined by measuring Th2 cytokine production. Isoliquiritigenin, 7, 4'-dihydroxyflavone (7, 4'-DHF) and liquiritigenin significantly suppressed IL-4 and IL-5 production in a dose-dependent manner, 7, 4'-DHF being most potent. It was also evaluated for effects on D10 cell proliferation, GATA-3 expression and IL-4 mRNA expression, which were suppressed, with no loss of cell viability. Chronic treatment with 7, 4'-DHF in a murine model of allergic asthma not only significantly reduced eosinophilic pulmonary inflammation, serum IgE levels, IL-4 and IL-13 levels, but also increased IFN-γ production in lung cell cultures in response to antigen stimulation.

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.

Pharmacology and immunological actions of a herbal medicine ASHMITM on allergic asthma

AbstractAllergic asthma is a chronic and progressive inflammatory disease for which there is no satisfactory treatment. Studies reported tolerability and efficacy of an anti‐asthma herbal medicine intervention (ASHMI) for asthma patients, developed from traditional Chinese medicine. To investigate the pharmacological actions of ASHMI on early‐ and late‐phase airway responses (EAR and LAR), Ovalbumin (OVA)‐sensitized mice received 6 weeks of ASHMI treatment beginning 24 h following the first intratracheal OVA challenge. EAR were determined 30 min following the fourth challenge and LAR 48 h following the last challenge. ASHMI effects on cytokine secretion, murine tracheal ring contraction and human bronchial smooth muscle cell prostaglandin (PG) production were also determined.ASHMI abolished EAR, which was associated with significantly reduced histamine, leukotriene C4, and OVA‐specific IgE levels, as well as LAR, which was associated with significantly reduced bronchoalveolar lavage fluid (BALF) eosinophils, decreased airway remodeling, and lower Th2 cytokine levels in BALF and splenocyte cultures. Furthermore, ASHMI inhibited contraction of murine tracheal rings and increased production of the potent smooth muscle relaxer PGI2. ASHMI abrogation of allergic airway responses is associated with broad effects on asthma pathological mechanisms. Copyright © 2009 John Wiley &amp; Sons, Ltd.

In Vitro Immunomodulatory Effect Of ASHMI (Anti-asthma Herbal Medicine Intervention) On PBMCs From Asthmatics

In Vitro Immunomodulatory Effect Of ASHMI (Anti-asthma Herbal Medicine Intervention) On PBMCs From Asthmatics

Safety and Tolerability of an Antiasthma Herbal Formula (ASHMI™) in Adult Subjects with Asthma: A Randomized, Double-Blinded, Placebo-Controlled, Dose-Escalation Phase I Study

Complementary and alternative medicines are increasingly used for the treatment of asthma in Western countries. A novel three-herb antiasthma herbal medicine intervention (ASHMI; Sino-Lion Pharmaceutical Company; Shan Dong China) was demonstrated to be effective and safe in a murine model of asthma and in a preliminary clinical study in China. The objective of this study was to evaluate the safety and tolerability of ASHMI in adult subjects with allergic asthma. Randomized, double-blind, placebo-controlled, dose escalation, phase I trial aimed at developing a botanical drug under the United States Food and Drug Administration Investigational New Drug title. Subjects received one of three doses of ASHMI or placebo: 600 mg (2 capsules); 1200 mg (4 capsules); or 1800 mg (6 capsules) twice daily for 1 week. Four (4) ASHMI and 2 placebo subjects were treated at each dose level. Subjects continued to use their conventional asthma medications for the duration of the study. Vital signs, physical examination, laboratory data, and electrocardiogram data were monitored throughout the study to assess occurrence of adverse events (AEs). Immunomodulatory studies were performed to evaluate the effect of ASHMI on cytokine, chemokine, and growth factor levels. Twenty (20) nonsmoking, allergic subjects with asthma were included in the study. Eight (8) subjects (4 ASHMI and 4 placebo) reported mild gastrointestinal symptoms. No grade 3 AEs were observed during the study period. Vital signs, electrocardiogram findings, and laboratory results obtained at pre- and post-treatment visits remained within normal range. No abnormal immunologic alterations were detected. In this phase I study, ASHMI appeared to be safe and well tolerated by subjects with asthma. These findings allowed initiation of a larger phase II study to assess the efficacy of ASHMI.

Development of an Efficient Fractionation Procedure for the Identification of Active Compounds in the Complex ASHMI (Anti-Asthma Herbal Medicine Intervention) Formula

RATIONALE: A targeted fractionation scheme was developed to simplify efforts aimed at identification of the chemical constituents most responsible for the therapeutic effects of ASHMI. The fractions showing the greatest inhibition of TNF-α release from LPS-stimulated macrophages were chosen for isolation and structural characterization studies.

Investigation of the Individual Herbs in ASHMI (Anti-Asthma Herbal Medicine Intervention) That is Most Responsible for Reducing IgE Secretion

Investigation of the Individual Herbs in ASHMI (Anti-Asthma Herbal Medicine Intervention) That is Most Responsible for Reducing IgE Secretion

Traditional Chinese medicine for the therapy of allergic disorders

The trend of increasing prevalence of allergic diseases in westernized countries poses a significant health problem and lasting cures for them are often not available. Many suffering from allergies and asthma seek alternative therapies including traditional Chinese medicines, fueling a surge in western interest in traditional Chinese herbal remedies. Information regarding the efficacy and safety of traditional Chinese herbal remedies is scant but studies appearing in English language journals are on the rise. This review summarizes the important publications focusing on traditional Chinese medicine therapies for allergic disorders in the year 2005. Very few studies describing well controlled clinical trials testing traditional Chinese herbal therapies for allergic diseases appeared in PubMed in 2005. Food allergy specifically does not seem to be a disorder traditionally recognized in the traditional Chinese medicine literature. Most in-vitro studies for anti-allergic properties of traditional Chinese herbs and formulas focus on mast cell inhibition. Clinical trials for anti-asthma traditional Chinese medicine formulas, anti-asthma herbal medicine intervention, anti-asthma herbal medicine intervention, and modified Mai Men Dong Tang, show promise as efficacious treatments for asthma. Food Allergy Herbal Formula-2 is a traditional Chinese medicine formula with good potential for a long-lasting treatment for food allergy. More rigorous studies are needed to fully elucidate the benefits and safety of traditional Chinese herbal medicines and the mechanisms that mediate their effects.

Efficacy and tolerability of antiasthma herbal medicine intervention in adult patients with moderate-severe allergic asthma

Chinese herbal medicine has a long history of human use. A novel herbal formula, anti-asthma herbal medicine intervention (ASHMI), has been shown to be an effective therapy in a murine model of allergic asthma. This study was undertaken to compare the efficacy, safety, and immunomodulatory effects of ASHMI treatment in patients with moderate-severe, persistent asthma with prednisone therapy. In a double-blind trial, 91 subjects underwent randomization. Forty-five subjects received oral ASHMI capsules and prednisone placebo tablets (ASHMI group) and 46 subjects received oral prednisone tablets and ASHMI placebo capsules (prednisone group) for 4 weeks. Spirometry measurements; symptom scores; side effects; and serum cortisol, cytokine, and IgE levels were evaluated before and after treatment. Posttreatment lung function was significantly improved in both groups as shown by increased FEV(1) and peak expiratory flow findings (P<.001). The improvement was slightly but significantly greater in the prednisone group (P<.05). Clinical symptom scores, use of beta(2)-bronchodilators, and serum IgE levels were reduced significantly, and to a similar degree in both groups (P<.001). T(H)2 cytokine levels were significantly reduced in both treated groups (P<.001) and were lower in the prednisone-treated group (P<.05). Serum IFN-gamma and cortisol levels were significantly decreased in the prednisone group (P<.001) but significantly increased in the ASHMI group (P<.001). No severe side effects were observed in either group. Anti-asthma herbal medicine intervention appears to be a safe and effective alternative medicine for treating asthma. In contrast with prednisone, ASHMI had no adverse effect on adrenal function and had a beneficial effect on T(H)1 and T(H)2 balance.