Beneficial effects of quercetin in COPD - a preliminary clinical trial

槲皮素对慢性阻塞性肺病的有益作用——初步临床试验

• 批准号: 8542760
• 负责人: MeiLan K Han
• 金额: $ 22.63万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8542760
• 关键词: 3-nitrotyrosine; Adrenal Cortex Hormones; Adverse effects; Agonist; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Apple; Asthma; Biological; Biological Availability; Biological Factors; Biological Markers; Breathing; Bronchial Hyperreactivity; Bronchodilator Agents; C-reactive protein; CCL18 gene; CD40 Ligand; Cause of Death; Chemicals; Chronic Obstructive Airway Disease; Chronic lung disease; Clara cell-specific protein; Clinical; Clinical Trials; Comorbidity; Data; Diet; Dietary Flavonoid; Disease; Dose; Drug Formulations; Epidemiologic Studies; Flavonoids; Food; Free Radicals; Frequencies; Future; Goals; High Pressure Liquid Chromatography; In Vitro; Inflammation; Inflammatory; Influenza; Intake; Intercellular adhesion molecule 1; Interleukin-6; Lung Inflammation; Lung diseases; Malondialdehyde; Measures; Monitor; Mus; Onions; Oral; Outcome; Oxidants; Oxidative Stress; Patients; Pharmaceutical Preparations; Physical Examination; Pilot Projects; Placebos; Plants; Plasma; Pneumonia; Procedures; Property; Proteins; Publishing; Pulmonary Sarcoidosis; Pulmonary Surfactant-Associated Protein D; Quercetin; Questionnaires; Reduced Glutathione; Research Personnel; Rhinovirus; Risk; Running; Safety; Serum; Severities; Smoking History; Spirometry; Sputum; Structure of parenchyma of lung; Supplementation; Symptoms; Testing; Therapeutic; Treatment Protocols; cytokine; dosage; fruits and vegetables; improved; in vivo; inflammatory marker; phenoxy radical; prevent; pulmonary function; response; volunteer

DESCRIPTION (provided by applicant): Quercetin, a plant flavonoid widely found in fruits and vegetables, is a potent antioxidant and anti- inflammatory. We recently showed that daily oral treatment with low levels of quercetin decreases oxidative stress, inflammation and prevents progression of lung disease in mice which display typical features of chronic obstructive lung disease (COPD) Our pilot studies also suggest that quercetin inhibits replication of rhinovirus, a major cause of COPD exacerbations. Finally, large epidemiological studies have suggested that a high- quercetin diet decreases the risk of COPD. Together, these data suggest that quercetin would be beneficial in the treatment of COPD. Nevertheless, key methodologic issues have not been resolved, including the dosage and frequency of supplementation, bioavailability, safety, dose-response relationship, or the appropriate biomarkers which reflect clinical outcomes in this disease. The overall goal of this application is to obtain the information necessary for large clinical trials in COPD. To accomplish this goal, we propose the following Specific Aims. 1. Determine if once-daily doses of quercetin are safe, acceptable and reach therapeutic concentrations in the plasma of patients with COPD. Using a quercetin formulation that has been "generally recognized as safe" by the FDA (Quercegen Pharma, Sudbury, MA), we will test the hypotheses that: 1) dietary flavonoid intake can be accurately monitored by questionnaire; and 2) daily supplementation of quercetin increases plasma quercetin levels in COPD patients; and 3) quercetin can be administered to patients with COPD of varying severity without adverse side effects. 2. Determine the effect of quercetin on oxidative stress, lung inflammation and pulmonary function in patients with COPD. We hypothesize that: 1) oxidative and inflammatory biomarkers can be safely and accurately measured in the serum and sputum of patients with COPD; 2) daily treatment with quercetin will reduce plasma and sputum markers of oxidative stress and inflammation; 3) daily treatment with quercetin will improve pulmonary function in patients with COPD. Results from these studies will provide data on the quercetin dosage and biological endpoints needed to carry out large clinical trials examining the efficacy of quercetin in COPD.

说明（由申请人提供）：槲皮素是一种广泛存在于水果和蔬菜中的植物类黄酮，是一种有效的抗氧化剂和抗炎剂。我们最近表明，每日口服低水平的槲皮素可以降低氧化应激，炎症，并防止小鼠肺部疾病的进展，这些小鼠表现出慢性阻塞性肺病（COPD）的典型特征。我们的初步研究还表明，槲皮素抑制鼻病毒的复制，这是COPD恶化的主要原因。最后，大型流行病学研究表明，高槲皮素饮食可降低COPD的风险。总之，这些数据表明，槲皮素将有利于COPD的治疗。然而，关键的方法学问题尚未解决，包括补充剂的剂量和频率、生物利用度、安全性、剂量-反应关系或反映该疾病临床结局的适当生物标志物。本申请的总体目标是获得COPD大型临床试验所需的信息。为了实现这一目标，我们提出以下具体目标。1.确定每日一次剂量的槲皮素是否安全，可接受，并在COPD患者的血浆中达到治疗浓度。使用已经被FDA（Quercegen Pharma，Sudbury，MA）“普遍认为是安全的”的槲皮素制剂，我们将测试以下假设：1）膳食类黄酮摄入可以通过问卷准确地监测;和2）每日补充槲皮素增加COPD患者的血浆槲皮素水平;和3）槲皮素可以施用于不同严重程度的COPD患者而没有不良副作用。2.确定槲皮素对COPD患者氧化应激、肺部炎症和肺功能的影响。我们假设：1）在COPD患者的血清和痰中可以安全准确地测量氧化和炎症生物标志物; 2）每天用槲皮素治疗将减少氧化应激和炎症的血浆和痰标志物; 3）每天用槲皮素治疗将改善COPD患者的肺功能。这些研究的结果将提供有关槲皮素剂量和生物学终点的数据，这些数据需要进行大型临床试验来检查槲皮素在COPD中的疗效。