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.

Licorice flavonoids inhibit eotaxin-1 secretion by human fetal lung fibroblasts in vitro.

Glycyrrhiza uralensis (Gan-Cao), commonly called "licorice", is one of the most commonly used herbs in traditional Chinese medicine (TCM). In the United States, licorice products are most often consumed as flavoring and sweetening agents in food products. The licorice triterpenoid glycyrrhizin has several biological activities, including anti-inflammatory activity. Other potential anti-inflammatory constituents in G. uralensis have not been fully investigated. Airway eosinophilic inflammation is a major feature of allergic asthma. Eotaxin-1 (eotaxin) is involved in the recruitment of eosinophils to sites of antigen-induced inflammation in asthmatic airways. Because human lung fibroblasts are the major source of eotaxin, inhibition of eosinophil recruitment by suppression of fibroblast eotaxin production is a potentially valuable approach for the pharmacological intervention in asthma. A systematic bioassay-guided purification of G. uralensis yielded five flavonoids: liquiritin, liquiritigenin, isoliquiritigenin, 7,4'-dihydroxyflavone, and isoononin. The structures of the compounds were established by (1)H and (13)C nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS) studies. The potential ability of these isolated pure compounds and glycyrrhizin to inhibit secretion of eotaxin-1 by human fetal lung fibroblasts (HFL-1) was tested. Liquiritigenin, isoliquiritigenin, and 7,4'-dihydroxyflavone were more effective than liquiritin, isoononin, and glycyrrhizin in suppressing eotaxin secretion. A concentration-response study showed the IC(50) concentrations of liquiritigenin, isoliquiritigenin, and 7,4'-dihydroxyflavone were 4.2, 0.92, and 0.21 microg/mL, respectively, demonstrating that Glycyrrhiza flavonoids inhibit eotaxin-1 secretion in vitro.