Botanicals for Chlamydia pneumonia infections-Revision 1

描述(申请人提供)：肺炎衣原体(CP)是一种细胞内的革兰氏阴性细菌，是一种重要的人类病原体，与5-10%的肺炎、支气管炎、哮喘和鼻窦炎病例有关。肺炎衣原体感染广泛传播，全世界50%-70%的成年人血清阳性。大量证据表明，慢性CP感染与动脉粥样硬化和冠心病(CHD)的发生和发展有关。仅在2002年，就有超过55份新的出版物表明慢性支气管炎与冠心病之间有很强的联系。目前已有多种抗生素用于CP感染的治疗，但CP难以根治，需要长期使用抗生素治疗。因此，抗生素耐药性和治疗失败是很常见的。因此，迫切需要新的方法来预防和治疗慢性CP感染。由于许多植物产品已经被用于治疗冠心病和感染已有数百年的历史，我们建议研究标准化植物提取物在CP及其慢性后遗症发病机制中的具体作用。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，并确定它们对动脉粥样硬化斑块发展的影响。为了实现这些目标，提取物将在体外进行测试，以确定对CP的活性，以及机理研究。只有最有效的提取物也将在动物模型中进行测试。在两年的时间里，12种植物提取物将在体外进行评估，6种将在体内进行评估。植物学的选择是基于使用Naprert数据库和其他文献来源的复杂数据分析的优先顺序。我们前期工作的数据表明，这个项目的假设和方法是科学合理的，因为一些传统用于治疗冠心病的提取物在体外已经显示出抗CP的活性。自那以后，这些提取物已经标准化(基于活性成分)以增强活性，并准备用于动物试验。这项建议是一项多学科合作，其长期目标是开发安全有效的标准化植物药物来预防/治疗CP感染，对动脉粥样硬化和冠心病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作为未来临床试验的基础。

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.