Beneficial effects of quercetin in COPD - a preliminary clinical trial

描述(申请人提供)：栎皮素，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药物。我们最近的研究表明，每天口服低水平的槲皮素可以减少小鼠的氧化应激、炎症和防止肺部疾病的进展，这些小鼠具有慢性阻塞性肺疾病(COPD)的典型特征。我们的初步研究还表明，Quercetin抑制鼻病毒的复制，鼻病毒是COPD病情恶化的主要原因。最后，大规模的流行病学研究表明，高含量的栎素饮食可以降低患COPD的风险。综上所述，这些数据表明，槲皮素对COPD的治疗是有益的。然而，关键的方法学问题还没有得到解决，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，或者反映这种疾病临床结果的适当的生物标志物。该应用程序的总体目标是获得COPD大型临床试验所需的信息。为实现这一目标，我们提出了以下具体目标。1.确定COPD患者血浆中每日一次剂量的槲皮素是否安全、可接受并达到治疗浓度。使用已被FDA(马萨诸塞州萨德伯里Quercegen Pharma)“普遍认为是安全的”的一种栎素配方，我们将检验以下假设：1)可以通过问卷准确监测饮食中的类黄素摄入量；2)每天补充槲皮素可提高COPD患者的血浆中的槲皮素水平；3)可以对不同严重程度的COPD患者使用槲皮素，而不会产生副作用。2.检测槲皮素对慢性阻塞性肺疾病患者氧化应激、肺部炎症及肺功能的影响。我们假设：1)COPD患者血清和痰中的氧化和炎症生物标志物可以安全和准确地测定；2)每天服用栎素会降低血浆和痰中氧化应激和炎症的标志物；3)每天服用栎素会改善COPD患者的肺功能。这些研究的结果将提供有关栎素剂量和生物终点的数据，这些数据需要进行大型临床试验来检验栎素对慢性阻塞性肺疾病的疗效。

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.