Asthma is a worldwide major public health problem, which currently affects 15 million people in the United States and the incidence is increasing. Although corticosteroids are widely used for asthma treatment, their side effects are a significant concern, particularly for children. A recent NIH Inner-city Asthma Study found that continuous daily treatment with inhaled corticosteroids had no long-term therapeutic benefit in terms of lung function, and new asthma medications, including leukotriene inhibitors and anti-lgE, have shown only marginal benefits. The need for safe and effective treatments of this disease is urgent. We previously reported that a 14 herb Chinese medicine formula, with immunomodulatory activity completely abrogated airway hyperreactivity in a murine model of asthma. This formula suppressed pro allergic inflammatory mediators secreted by Th2 lymphocytes without causing the overall immunbsupression produced by corticosteroids. We have now developed an equally effective formula-ASHMI-, which contains only three herbs. We have established HPLC fingerprints of this formula for quality control purposes. We propose to use ASHMI in three highly interactive projects whose over all goal is to assess the potential use of Chinese herbal therapy for allergic asthma. Project #1 will focus on investigating the pharmacological effects and immunotherapeutic mechanisms underlying the therapeutic effect of ASHMI using a murine model of chronic asthma, ex vivo tracheal ring segments, and in vitro Th2 memory lymphocytes. Project #2 will assess the effect of ASHMI treatment on atopic patients with moderate to severe persistent asthma. Project #3 will investigate possible synergy or potentiation both between the three herbal components, and between the constituents of each individual herb, to determine which constituents of the formula are most likely responsible for ASHMI's various biological effects, to chemically characterize these constituents, and to characterize, in mice, the pharmacokinetics of relevant biologically active constituents of ASHMI. These highly interdependent programs will be supported by an administrative core facility. The interactive nature of the projects proposed and the close collaboration between project leaders and their laboratories provide a unique opportunity to focus institutional strengths on developing therapies for this common disease. The integrated findings of each project of this center grant will provide experimental and clinical bases regarding the efficacy and safety of ASHMI for asthma treatment and may ultimately lead to a novel therapy for asthma, as well as advance our understanding of the pharmacological, immunological and molecular mechanisms underlying the therapeutic effects of ASHMI on allergic asthma.
Showing the most recent 10 out of 27 publications
