Ming-Chun Wen

Glycyrrhiza uralensis flavonoids present in anti-asthma formula, ASHMI™, 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. Copyright

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

Allergic 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.

The potential use of Chinese herbal medicines in treating allergic asthma

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.

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

OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION By comparing the interaction index values, we find that constituents in ASHMI(TM) synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.