## 4 Discussion  
Asthma is one of the most common and complex chronic respiratory disorder with airway inflammation as a main cause. Various types of tissues and cells are involved in the pathophysiology of asthma. Airway epithelial cells are the first barrier in the lung as opposed to foreign antigens inducing inflammation and when it fails, sustained inflammation can worsen the symptoms of asthma and result in exacerbation. Chemokines from airway epithelial cells, such as eotaxins and RANTES, have been described to contribute to chronic airway inflammation by recruiting macrophages, eosinophils, and Th cells at the site of inflammation [24; 25; 26; 27; 28; 29]. In our study, JGTW demonstrated potent inhibitory effects on the generation of inflammatory chemokines in IT-stimulated BEAS-2B cells, a widely used in vitro model of airway epithelial cells. In addition, the JGTW treatment effectively suppressed MMP-9 activity, an  
Figure 9: Effect of JGTW on Th2 cytokines and IgE levels in OVA-induced mice. The levels of Th2 cytokines and IgE were determined by ELISA kits. Th2 cytokines: IL-5 (**A**) and IL-13 (**B**). IgE: total IgE (**C**) and OVA-specific IgE (**D**). The values are presented as mean \(\pm\) SEM. \(\#\)\(p<0.05\) or \(\#\)\(p<0.01\) versus NC group; and \(*\)\(p<0.05\) or \(**\)\(p<0.01\) versus OVA-induced group. enzyme that degrades extracellular matrix proteins, and infiltrating inflammatory effector cells [30,31], in IT-stimulated BEAS-2B cells. It is a well-known fact that the increased expression of ICAM-1 and VCAM-1 on the respiratory epithelial cells is an important foundation of inflammatory cell infiltration into the inflamed airways [32], resulting in the development of asthma. JGTW treatment significantly suppressed the increased expression of these mediators in BEAS-2B cells stimulated with IT. Collectively, these findings demonstrated that JGTW had anti-inflammatory function acting through downregulation of pro-inflammatory soluble mediator expression, decreasing MMP-9 activity, resulting in lowered expression of adhesion molecules in a pulmonary epithelial cell model. It is well known that eosinophils and mast cells are key players in the pathophysiology of asthma; however, evidence for the importance of macrophage-mediated inflammation in asthma is emerging [8,9,33]. High levels of macrophages are found in lung tissues in both asthma patients and mice with experimental asthma [33,34]. In our study, LPS-stimulated RAW264.7 cells are used to mimic the inflammatory responses of macrophages. LPS treatment markedly increased iNOS expression, a widely used marker for inflammation, in RAW264.7 cells and pretreatment with JGTW for 1 h efficiently blocked this elevated expression of iNOS. In line with this result, JGTW also suppressed nitrite production in LPS- stimulate RAW264.7 cells. It is also reported that JGTW significantly decreased prostaglandin E2 production via suppressing COX-2, IL-1, and IL-6, which are known mediators of airway inflammation in asthma [13]. Collectively, our data and others suggested that JGTW alleviates the inflammatory response by reducing various mediators such as iNOS, COX2, and cytokine expression. It is known that the MAPK and NF-kB signaling pathways are an important part in mediating the pathophysiology of asthma, and these signaling pathways are also associated with the activation of effector cells during inflammation [35,36]. Hence, the inhibitory effect of JGWT on aberrant MAPK activation in LPS-stimulated RAW264.7 cells was assessed. JGTW efficiently suppressed the phosphorylation of p38 and ERK. Furthermore, JGTW exerted an inhibitory effect on the activation of NF-kB signaling, showing decreased expression of phosphorylated-NF-kB p65 subunit and \(\mathrm{lxB\alpha}\). These results suggest that the inhibition of iNOS expression and anti-inflammatory properties by JGTW is mediated via suppression of NF-kB activation at least partly through p38 and ERK suppression.