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部疾病，是世界范围内的主要公共卫生问题，目前在美国影响着1500万人。虽然皮质类固醇广泛用于哮喘治疗，但其副作用是一个重大问题，特别是对儿童。迫切需要对这种疾病进行安全有效的治疗。中草药疗法（CHT）已经使用了数千年，被认为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，因为很少有对照良好的科学研究证明其有效性、安全性和作用机制。在我们的R21资助期间，我们从原始的抗哮喘配方msm -002（由14种草药组成）衍生出了哮喘草药干预ASHMI（由3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。我们在一个具有良好特征的慢性过敏性哮喘小鼠模型中证明，ASHMI对哮喘的主要发病机制（包括AHR、肺部炎症、气道重塑）具有广泛的治疗作用，这些作用与ASHMI下调Th2反应有关，这表明ASHMI有可能成为一种哮喘治疗药物。在本项目中，我们将深入评价中药方剂ASHMI对小鼠变应性哮喘模型的治疗作用及其机制。对AHR、炎症、气道重塑、气道平滑肌收缩和效应记忆T细胞细胞因子分泌的药理作用以及持久的治疗效果将通过体内和体外的一系列生理、免疫学和分子生物学测量来确定。因为我们已经确定该配方以无毒的方式抑制Th2细胞因子的分泌，我们将通过关注Th2转录因子GATA-3来研究这种作用的分子机制。与项目#3合作，我们将研究ASHMI提取物中单个生物活性成分并评估其对过敏性气道反应的协同作用。本研究的完成对于验证中药对变应性哮喘可能的药理作用，深入了解ASHMI治疗变应性哮喘的免疫治疗机制具有重要意义。最终，这项研究以及本中心资助的其他项目的研究可能会导致一种新的方法——植物性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.