To Study the Effect of Ding Chuan Tang on Reducing Airway Hyper-Responsiveness and Inflammasome Activity in Asthmatic Mouse Model

Bronchial asthma is a chronic inflammatory disorder with airways hyperresponsiveness (AHR), smooth muscle hypertrophy, remodeling and eosinophil infiltration. In addition to over-activated Th2 and mast cells, elevated levels of eotaxins, TNF-, IL-1, nitric oxide (NO), and other inflammatory cytokines and chemokines in lung tissues have been linked to the severity of asthma. Other airway diseases, including idiopathic pulmonary fibrosis (IPF) or acute inflammation can also be induced with bleomycin (BLM) or lipopolysaccharide (LPS), respectively. The activity of inflammasomes and extracellular ATP have recently been reported to correlate with the pathogenesis of asthma and airway inflammatory disorders, particular the purinergic P2X7 receptor and its related molecules, include NLRP3, Pannexin-1, and IL-33. Although conventional medicine may apply bronchial dilators or steroids to those patients, traditional Chinese medicine (TCM) has been persuaded by a large number of patients who are suffered with airway disorders. However, solid scientific evidence with the use of TCM has not been available, particularly concern related to toxicity, doses and frequency, and pharmacological mechanisms. Our previous studies indicate that the Din Chuan Tang (DCT, a Chinese herb decoction) improved the airway hypersensitiveness in a double-blind and placebo-controlled clinical trial and ovalbumin (OVA)-induced asthmatic murine model. Some of the indicating compounds, such as glycyrrhizin, baicalin, or baicalein have been shown to have anti-inflammatory efficacy. Based on our preliminary results for available animal models with OVA-induced asthma, BLM- or LPS-induced airway inflammatory models, we would further examine the potential mechanism of DCT or some of the indicating compounds on mice of those lung inflammation models. The effect of the tested drugs on the inflammatory mediators or the activity of inflammasome components in lung tissues of the treated mice will be extensively examined. Moreover, we will also examine the activity of inflammasome components, signal transduction pathways and the transcription factors in human lung epithelial BEAS-2B cells to elucidate the detailed mechanisms of DCT and these indicating compounds. The results will also provide the scientific significance at molecular level for TCM. Other studies related to potential compounds isolated from nature products will also be benefited with these models. Moreover, the results will serve as the reference information for future clinical trials related to TCM.

Project ID:PC10406-0227
External Project ID:MOST104-2320-B182-005