Asthma, a chronic inflammatory lung disease, is a worldwide major public health problem, which currently affects 15 million people in the United States. Although corticosteroids are widely used for asthmatreatment, their side effects are a significant concern, particularly for children. The need for safe and effective treatments of this disease is urgent. Chinese herbal therapy (CHT)used for thousands of years, has been suggested to have a potential for treating allergies and asthma. However, a role for CHT in asthmatherapy remains to be established because there are few well-controlled scientific studies demonstrating its efficacy, safety and mechanisms of action. During our R21 grant period we generated an asthma herbal medicine intervention ASHMI (composed of 3 herbs) derived from the original anti asthma formula MSSM-002 (composed of 14 herbs). This development makes herbal formula quality control less difficult. We demonstrated in a well-characterized murine model of chronic allergic asthma that ASHMI exhibits a broad spectrum of therapeutic effects on the major pathogenesis of asthma, including AHR, pulmonary inflammation, airway remodeling, which was associated with its down-regulation Th2 responses, indicating a potential for developing as an asthma therapy. In this project, we will evaluate in depth the therapeutic effects and mechanisms of the herbal formula ASHMI on a well-characterized murine model of allergic asthma. Pharmacological effects on AHR, inflammation, airway remodeling, airway smooth muscle contractility, and effector memory T cell cytokine secretion as well as a long lasting therapeutic effect will be determined using a range of physiological, immunological and molecular biology measurements in vivo and in vitro. Because we have determined that this formula suppresses Th2 cytokine secretion in a non-toxic manner, we will investigate the molecular mechanisms underlying the effect by focusing on the Th2 transcription factor GATA-3. In collaboration with Project #3, we will investigate individual bioactive constituents and assess their synergistic effects in ASHMI extract on allergic airway responses. Accomplishing this study will be of fundamental importance to validate the possible pharmacologicalactions of Chinese herbal medicine on allergic asthma, and provide advanced understanding of the immunotherapeutic mechanisms underlying ASHMI effects on allergic asthma. Ultimately, this study along with the studies addressed in other projects of this center grant may lead to a novel approach-botanical drug for treating asthma and perhaps other allergic inflammatory disease.
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