Botanicals for Chlamydia pneumonia infections-Revision 1

治疗肺炎衣原体感染的植物药 - 第 1 版

• 批准号: 6721086
• 负责人: GAIL B MAHADY
• 金额: $ 19.03万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6721086
• 关键词: Chlamydiaceae; antibiotics; atherosclerotic plaque; cardiovascular disorder prevention; cell adhesion molecules; chemoprevention; chlamydial disease; combination chemotherapy; disease /disorder model; drug design /synthesis /production; drug discovery /isolation; drug screening /evaluation; genetically modified animals; interdisciplinary collaboration; laboratory mouse; medicinal plants; microorganism disease chemotherapy; nonhuman therapy evaluation; pharmacokinetics; plant extracts

DESCRIPTION (provided by applicant): Chlamydia pneumonia (CP), an intracellular gram-negative bacterium, is a significant human pathogen linked with 5-10% of cases of pneumonia, bronchitis, asthma and sinusitis. Infection with CP is wide spread with 50-70% of adults worldwide being seropositive. A substantial body of evidence has linked chronic CP infections with the development and progression of atherosclerosis and coronary heart disease (CHD). In 2002 alone over 55 new publications have indicated a strong association between CP and CHD. A variety of antibiotics have been used for the treatment of CP infections, however CP is difficult to eradicate, and requires long-term antibiotic therapy. Thus, antibiotic resistance and treatment failures are common. Therefore new approaches to the prevention and treatment of chronic CP infections are urgently needed. Since many botanical products have been used for centuries for the treatment of CHD and infections, we are proposing to investigate the specific effects of standardized botanical extracts on the pathogenesis of CP and its chronic sequelae. The primary goal of the project is to test standardized botanical extracts and combinations of extracts for the prevention and treatment of CP infections, and determine their impact on atherosclerotic plaque development. To accomplish these goals, the extracts will be tested in vitro to determine activity against CP, as well mechanistic studies. Only the most active extracts will also be tested in an animal model. Over the two-year period 12 botanical extracts will be evaluated in vitro and six in vivo. Botanical selection was based on prioritization using complex data analysis of the Napralert database and other literature sources. Data from our preliminary work demonstrates that the hypothesis and methods for this project are scientifically sound, as a number of extracts used traditionally for the treatment of CHD have already shown activity against CP in vitro. These extracts have since been standardized (based on the active constituents) to enhance the activity, and are ready for animal testing. This proposal is a multidisiplinary collaboration with the long-term objective of developing safe and effective standardized botanicals for the prevention/treatment of CP infections, with overall impact on the development of atherosclerosis and CHD. Data and active standardized extracts developed during this work will be used as the basis for future clinical trials.

描述（由申请人提供）：肺炎衣原体（CP）是一种细胞内革兰氏阴性细菌，是一种重要的人类病原体，与5-10%的肺炎、支气管炎、哮喘和鼻窦炎病例相关。CP感染广泛传播，全世界50-70%的成年人血清反应阳性。大量证据表明慢性CP感染与动脉粥样硬化和冠心病（CHD）的发生和进展有关。仅在2002年，就有超过55篇新的出版物表明CP和CHD之间有很强的关联。多种抗生素已用于治疗CP感染，但CP难以根除，需要长期抗生素治疗。因此，抗生素耐药性和治疗失败是常见的。因此，迫切需要预防和治疗慢性CP感染的新方法。由于许多植物产品已被用于治疗冠心病和感染了几个世纪，我们建议调查的具体影响，标准化的植物提取物对CP的发病机制及其慢性后遗症。该项目的主要目标是测试用于预防和治疗CP感染的标准化植物提取物和提取物组合，并确定其对动脉粥样硬化斑块发展的影响。为了实现这些目标，将在体外测试提取物以确定对CP的活性以及机制研究。仅在动物模型中测试最具活性的浸提液。在为期两年的时间里，将对12种植物提取物进行体外评价，对6种植物提取物进行体内评价。植物选择的基础上优先使用复杂的数据分析Napralert数据库和其他文献来源。来自我们初步工作的数据表明，该项目的假设和方法在科学上是合理的，因为传统上用于治疗CHD的一些提取物已经显示出体外抗CP的活性。这些提取物已被标准化（基于活性成分），以提高活性，并准备进行动物试验。该提案是一项多学科合作，长期目标是开发安全有效的标准化植物药，用于预防/治疗CP感染，对动脉粥样硬化和CHD的发展产生全面影响。在这项工作中开发的数据和活性标准化提取物将用作未来临床试验的基础。