Center for Chinese Herbal Therapy (CHT) for Asthma

描述（由申请人提供）：哮喘是一种慢性炎症性肺病，是一个全球性的主要公共卫生问题，目前影响美国1500万人。虽然皮质类固醇广泛用于哮喘治疗，但其副作用是一个值得关注的问题，特别是对儿童。对这种疾病的安全和有效治疗的需求是迫切的。中国草药疗法（CHT）使用了数千年，已被认为具有治疗过敏和哮喘的潜力。然而，CHT在哮喘治疗中的作用仍有待确定，因为很少有控制良好的科学研究证明其疗效，安全性和作用机制。在我们的R21资助期间，我们产生了一种哮喘草药干预ASHMI（由3种草药组成），它来自原始的抗哮喘配方MSSM-002（由14种草药组成）。这一发展使得草药配方的质量控制变得不那么困难。我们在慢性过敏性哮喘的小鼠模型中证明，ASHMI对哮喘的主要发病机制（包括AHR、肺部炎症、气道重塑）表现出广谱的治疗作用，这与其下调Th 2应答相关，表明其具有开发为哮喘治疗的潜力。在这个项目中，我们将深入评估草药配方ASHMI对过敏性哮喘小鼠模型的治疗效果和机制。将使用一系列体内和体外生理学、免疫学和分子生物学测量来确定对AHR、炎症、气道重塑、气道平滑肌收缩性和效应记忆T细胞细胞因子分泌的药理学作用以及持久的治疗效果。因为我们已经确定该配方以无毒的方式抑制Th 2细胞因子分泌，我们将通过关注Th 2转录因子加塔-3来研究该作用的分子机制。与项目#3合作，我们将研究单个生物活性成分，并评估它们在ASHMI提取物中对过敏性气道反应的协同作用。本研究的完成对于验证中草药对过敏性哮喘的可能药理作用以及进一步了解ASHMI对过敏性哮喘的免疫学机制具有重要意义。最终，这项研究沿着该中心资助的其他项目的研究可能会导致一种新的方法-植物药物治疗哮喘和其他过敏性炎症疾病。

DESCRIPTION (provided by applicant): 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 asthma treatment, 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 asthma therapy 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 pharmacological actions 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.