Center for Chinese Herbal Therapy (CHT) for Asthma

哮喘是一个世界性的重大公共卫生问题，目前在美国影响着1500万人，而且发病率还在增加。虽然皮质类固醇被广泛用于哮喘治疗，但它们的副作用是一个重要的问题，特别是对儿童。NIH内城哮喘最近的一项研究发现，从肺功能的角度来看，持续的每日吸入皮质类固醇治疗对肺功能没有长期的治疗益处，而包括白三烯抑制剂和抗LGE在内的新的哮喘药物仅显示出微乎其微的益处。迫切需要对这种疾病进行安全有效的治疗。我们之前曾报道过，一种具有免疫调节活性的14种草药配方完全消除了哮喘小鼠模型的气道高反应性。该配方抑制了Th2淋巴细胞分泌的促过敏性炎症介质，而不会引起皮质类固醇产生的整体免疫抑制。我们现在已经开发出一个同样有效的配方--阿什米--它只包含三个 草药。为了进行质量控制，我们已经建立了该配方的高效液相指纹图谱。我们建议在三个高度互动的项目中使用Ashmi，这三个项目的总体目标是评估中药治疗过敏性哮喘的潜在用途。项目1将侧重于使用慢性哮喘小鼠模型、体外气管环段和体外Th2记忆淋巴细胞来研究Ashmi的药理作用和免疫治疗机制。项目2将评估Ashmi治疗中度至重度持续性哮喘的特应性患者的效果。项目3将调查三种草药成分之间以及每种草药成分之间可能的协同或增强作用，以确定配方中哪些成分最有可能对阿什米的各种生物学作用负责，对这些成分进行化学表征，并在小鼠身上表征阿什米相关生物活性成分的药代动力学。这些高度相互依存的方案将得到一个行政核心设施的支持。拟议项目的互动性以及项目领导人与其实验室之间的密切合作提供了一个独特的机会，可以将机构力量集中在开发这种常见疾病的治疗方法上。该中心资助的每个项目的综合结果将为Ashmi治疗哮喘的有效性和安全性提供实验和临床基础，并最终可能导致一种新的哮喘治疗方法，并促进我们对Ashmi治疗过敏性哮喘的药理学、免疫学和分子机制的理解。

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.