licochalcone-a and Asthma

Topics: Animals; Antibody Specificity; Asthma; Bronchoalveolar Lavage Fluid; Cell Adhesion; Chalcones; Chemokines; Collagen; Cyclooxygenase 2; Disease Models, Animal; DNA Damage; Eosinophils; Female; Glutathione; Goblet Cells; Humans; Hyperplasia; Inflammation Mediators; Lung; Malondialdehyde; Mice, Inbred BALB C; Ovalbumin; Oxidative Stress; Protective Agents; Reactive Oxygen Species; Respiratory Hypersensitivity; THP-1 Cells

Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodeling, which is associated with increased airway smooth muscle (ASM) mass. Licochalcone A is the predominant characteristic chalcone in licorice root. We found that licochalcone A inhibited vascular endothelial growth factor (VEGF)-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed via inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activity, but not that of Akt. Furthermore, licochalcone A treatment inhibited VEGF-induced activation of VEGF receptor 2 (VEGFR2) and ERK and blocked the downregulation of caveolin-1 in a concentration-dependent manner. Collectively, our findings suggested that licochalcone A inhibited VEGF-induced ASM cell proliferation by suppressing VEGFR2 and ERK1/2 activation and downregulating caveolin-1. Further studies of these mechanisms are needed to facilitate the development of treatments for smooth muscle hyperplasia-associated diseases of the airway, such as asthma.

Topics: Asthma; Caveolin 1; Cell Proliferation; Cells, Cultured; Chalcones; Humans; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Myocytes, Smooth Muscle; Respiratory System; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

Asthma is a common chronic inflammatory disease characterized by the infiltration and accumulation of memory-like Th2 cells and eosinophils. Viral infection has emerged as the most common cause of severe episodes of asthma. For the treatment of bronchial asthma, the root of liquorice (Glycyrrhiza glabra) has been used as a traditional medicine in the East and West. Licochalcone A is the predominant, characteristic chalcone in liquorice root. To determine whether licochalcone A possesses an anti-inflammatory effect, we tested its effect on the expression and production of thymic stromal lymphopoietin (TSLP) in BEAS 2B cells and primary bronchial epithelial cells. We found that polyinosinic-polycytidylic acid (poly-IC)-induced TSLP expression was suppressed by treatment with licochalcone A in a dose- and time-dependent manner. We also found that poly-IC-induced mRNA expression of other proinflammatory mediators such as MCP-1, RANTES, and IL-8 was suppressed by licochalcone A. Furthermore, licochalcone A suppressed poly-IC-induced nuclear factor kappa B (NF-κB) nuclear translocation and DNA-binding activity by suppressing the Iκβ kinase (IKK) activity but not by direct phosphorylation of p65 at serine 276. Collectively, our findings suggest that licochalcone A suppresses poly-IC-induced TSLP expression and production by inhibiting the IKK/NF-κB signaling pathway, which might be involved in the pathogenesis of virus-exacerbated asthma. Further elucidation of the mechanisms underlying these observations can help develop therapeutic strategies for virally induced asthma.

Topics: Anti-Inflammatory Agents; Asthma; Cells, Cultured; Chalcones; Cytokines; Gene Expression Regulation; Humans; Thymic Stromal Lymphopoietin

Licochalcone A (Lico A) is a major and biogenetically characteristic chalcone isolated from the root of Xinjiang liquorice, Glycyrrhiza inflata.. We focused on investigating whether Lico A possesses distinct anti-inflammatory activity on a non-infectious mouse model of asthma, and we aimed to elucidate its involvement with the mitogen-activated protein kinases pathway.. BALB/c mice that were sensitized and challenged to ovalbumin (OVA) were treated with Lico A (50 mg/kg) 1 h before they were challenged with OVA.. Our study demonstrated that Lico A may effectively inhibit the increase in T-helper type 2 cytokines, such as interleukin (IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid, and reduced serum levels of OVA-specific IgE and IgG. Furthermore, Lico A substantially inhibited OVA-induced eosinophilia in lung tissue and mucus hyper-secretion by goblet cells in the airway. Meanwhile, pretreatment with Lico A resulted in a significant reduction in mRNA expression of acidic mammalian chitinase, chitinase 3-like protein 4 (Ym2), E-selectin, Muc5ac, CCL11 and CCR3 in lung tissues and airway hyper-responsiveness to methacholine.. These findings suggest that Lico A may effectively delay the progression of airway inflammation and could be used as a therapy for patients with allergic airway inflammation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Chalcones; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Immunoglobulin E; Immunoglobulin G; Lung; Mice; Mice, Inbred BALB C; Receptors, CCR3