Center for Chinese Herbal Therapy (CHT) for Asthma

哮喘中药治疗中心 (CHT)

• 批准号: 7288396
• 负责人: Xiu-Min Li
• 金额: $ 110.27万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7288396
• 关键词: Center; Chinese; Herbal; Therapy; CHT

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.

描述（由申请人提供）：哮喘是一种慢性炎症性肺部疾病，是一个世界范围内的重大公共卫生问题，目前影响着美国 1500 万人。尽管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，特别是对于儿童而言。迫切需要安全有效地治疗这种疾病。中草药疗法 (CHT) 使用了数千年，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，因为很少有严格对照的科学研究证明其功效、安全性和作用机制。在我们的 R21 资助期内，我们从原始抗哮喘配方 MSSM-002（由 14 种草药组成）衍生出哮喘草药干预 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更加困难。我们在一个充分表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表现出广泛的治疗作用，包括 AHR、肺部炎症、气道重塑，这与其下调 Th2 反应相关，表明具有开发哮喘治疗的潜力。在这个项目中，我们将深入评估草药配方 ASHMI 对特征明确的过敏性哮喘小鼠模型的治疗效果和机制。对 AHR、炎症、气道重塑、气道平滑肌收缩力和效应记忆 T 细胞细胞因子分泌的药理作用以及长期持续的治疗效果将通过一系列体内和体外生理、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，所以我们将重点关注 Th2 转录因子 GATA-3，研究其作用的分子机制。与项目 #3 合作，我们将研究 ASHMI 提取物中的各个生物活性成分，并评估它们对过敏性气道反应的协同作用。完成这项研究对于验证中草药治疗过敏性哮喘的可能药理作用，并深入了解 ASHMI 对过敏性哮喘的免疫治疗机制具有重要意义。最终，这项研究以及该中心资助的其他项目中进行的研究可能会产生一种新的方法——治疗哮喘和其他过敏性炎症疾病的植物药物。