Plant Polyphenols for the Treatment of Chronic Obstructive Pulmonary Disease

植物多酚治疗慢性阻塞性肺疾病

基本信息

批准号：
7876954
负责人：
EDWARD JAMES KENNELLY
金额：
$ 28.53万
依托单位：
HERBERT H. LEHMAN COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7876954
关键词：
Animal Model Anthocyanins Anti-Inflammatory Agents Anti-inflammatory Antioxidants Area Biological Biological Assay Blueberries Bronchodilator Agents Cell Culture Techniques Cells Chronic Chronic Obstructive Airway Disease Cigarette Complex Data Development Diet Educational workshop Epithelial Cells Ericaceae Eugenia Family Fruit Funding Glucosides Goals Grant In Vitro Inflammation Inflammatory Interleukin-8 Laboratories Lead Lung Lung diseases Mentored Clinical Scientist Development Award (K08)Modeling Myrtaceae Myrtus Obstruction Oxygen Patients Peptide Hydrolases Plants Prevention Prostaglandin-Endoperoxide Synthase Publications Reactive Oxygen Species Research Risk Smoke Source Steroid Resistance Steroids Structure of parenchyma of lung System Testing Therapeutic Therapeutic Agents United States National Institutes of Health Universities Work Writing base career cigarette smoke-induced cigarette smoking delphinidin diphenyl drug discovery effective therapy fruits and vegetables in vitro Assay in vitro testing in vivo men mouse model novel novel therapeutics plant growth/development polyphenol research study respiratory response skills

项目摘要

DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) is a respiratory condition characterized by irreversible airflow obstruction due to chronic inflammation. Cigarette smoke is the main etiologic factor associated with the development of COPD, for which there is no cure. Although bronchodilators and steroids are used in the treatment of COPD, only oxygen has been demonstrated to prolong survival of patients. Antioxidants and anti-inflammatory agents may be useful in the treatment of COPD. Many edible fruits are rich sources of polyphenolic antioxidants and anti-inflammatory compounds, and diets rich in fruits and vegetables are correlated with a reduced risk of COPD in men. Our preliminary data demonstrate that two plant-derived polyphenols, the novel depside jaboticabin and the anthocyanin delphinidin 3-glucoside, both from the Brazilian fruit Myrciaria cauliflora, have antioxidant and anti-inflammatory activities. Jaboticabin and delphinidin 3-glucoside both inhibit interleukin-8 induction in cells exposed to cigarette-smoke extract. We hypothesize that polyphenols, like jaboticabin and delphinidin 3-glucoside, will modulate the cigaretteinduced inflammatory, oxidative, and proteolyitic responses of the lung. We will test this by isolating a group of polyphenols from four edible fruits in the Ericaceae (blueberry) and Myrtaceae (myrtle), plant families rich in polyphenols. The purified polyphenols will be tested in vitro using antioxidant assays including 2,2- diphenyl-1-picrylhydrazyl and oxygen radical absorbance capacity, and anti-inflammatory assays for IL-8 and cyclooxygenase. The polyphenols will be prioritized for further study based on the activity in these assays as well as their structural uniqueness. Three of the polyphenols will undergo further mechanistic studies. The results will be used to select the most promising compound that will be tested in an in vivo animal model for COPD. This model has proved to be valuable in identifying causative mechanisms of COPD, and also provides an essential vehicle for drug discovery. An additional aim of this project is for the PI to participate in career developmental activities to make him more competitive for NIH R01 funding. We anticipate that the project will lead to the discovery of new and/or potent polyphenols that will serve as models for new therapeutic agents for the prevention and/or treatment of COPD.

描述（由申请人提供）：慢性阻塞性肺病（COPD）是一种呼吸系统疾病，其特征是由于慢性炎症导致不可逆的气流阻塞。香烟烟雾是导致慢性阻塞性肺病（COPD）的主要病因，目前尚无治愈方法。尽管支气管扩张剂和类固醇用于治疗慢性阻塞性肺病，但只有氧气已被证明可以延长患者的生存期。抗氧化剂和抗炎剂可用于治疗慢性阻塞性肺病。许多可食用水果富含多酚抗氧化剂和抗炎化合物，富含水果和蔬菜的饮食与降低男性患慢性阻塞性肺病的风险相关。我们的初步数据表明，两种植物源性多酚，即新型缩酚酸 jaboticabin 和花青素飞燕草素 3-葡萄糖苷，均来自巴西水果 Myrciaria cauliflora，具有抗氧化和抗炎活性。 Jaboticabin 和 delphinidin 3-glucoside 均能抑制暴露于香烟烟雾提取物的细胞中白细胞介素 8 的诱导。我们假设多酚，如 Jaboticabin 和飞燕草素 3-葡萄糖苷，将调节香烟引起的肺部炎症、氧化和蛋白水解反应。我们将通过从富含多酚的植物杜鹃花科（蓝莓）和桃金娘科（桃金娘）的四种可食用水果中分离出一组多酚来对此进行测试。纯化的多酚将使用抗氧化剂测定（包括 2,2-二苯基-1-三硝基苯肼和氧自由基吸收能力）以及 IL-8 和环氧合酶的抗炎测定进行体外测试。根据这些测定中的活性及其结构独特性，多酚将优先进行进一步研究。其中三种多酚将进行进一步的机理研究。结果将用于选择最有前途的化合物，并在慢性阻塞性肺病的体内动物模型中进行测试。该模型已被证明对于确定 COPD 的致病机制很有价值，并且还为药物发现提供了重要的工具。该项目的另一个目标是让 PI 参与职业发展活动，使他在获得 NIH R01 资助时更具竞争力。我们预计该项目将导致新的和/或有效的多酚的发现，这些多酚将作为预防和/或治疗慢性阻塞性肺病的新治疗剂的模型。