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 ¹H and ¹³C 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 IC₅₀ concentrations of liquiritigenin, isoliquiritigenin, and 7,4′-dihydroxyflavone were 4.2, 0.92, and 0.21 μg/mL, respectively, demonstrating that Glycyrrhiza flavonoids inhibit eotaxin-1 secretion in vitro.