Unraveling Immunostimulatory and Immunosuppressive Effects of Echinacea purpurea

描述(由申请人提供)：疾病控制中心报告称，紫锥菊是美国第三大最常用的草药。紫锥菊通常用于治疗上呼吸道感染，这种感染每年困扰成年人两到四次，每年的医疗费用超过100亿美元。几种紫锥菊制剂及其成分已显示出抑制炎症的能力，因此可能被用于治疗上呼吸道感染的症状。虽然紫锥菊在一些早期试验中显示出了实现这一目的的希望，但最近的一些临床试验表明，某些紫锥菊提取物对治疗上呼吸道感染无效。这些相互矛盾的发现至少部分可以由紫锥菊研究中使用的研究材料的组成的几个问题来解释。关于紫锥菊的哪些特定成分是抗炎作用的合适标记物，仍然缺乏知识。此外，在复杂的紫锥菊提取物中存在的许多成分中，有几种可以刺激免疫反应，这一活动在治疗上呼吸道感染症状时很可能是不受欢迎的。另一个复杂的因素是，这些免疫刺激成分可能是由内生细菌产生的，内生细菌生活在紫锥菊植物中。通过拟议的研究，我们试图展示抗炎紫锥菊制剂的理想成分分布，并展示去除刺激免疫反应的成分的程序。为了实现这一目标，我们将采用我们的研究实验室最近开发的一种方法--协同导向分馏，它使粗提物中特定成分的存在与生物活性联系在一起。这种方法可以用来识别复杂混合物中协同、相加或拮抗相互作用的成分。作为我们研究的结果，我们希望能够对用于科学研究或治疗上呼吸道感染的紫锥菊提取物进行更有效的质量控制。 公共卫生相关性：该项目与公共卫生相关，因为它涉及对广受欢迎的植物药物紫锥菊的调查，紫锥菊被用于治疗感冒和流感等上呼吸道感染。据估计，美国每年有3万人死于甲型流感。通过拟议的研究，我们试图为紫锥菊制剂的生产提供更好的疗效，以治疗此类感染。

DESCRIPTION (provided by applicant): The Centers for Disease Control reports that Echinacea is the third most commonly used herbal medicine in the US. Echinacea is typically employed for treatment of upper respiratory infections, which afflict adults two-four times per year, and cost over $10 billion in annual medical costs. Several Echinacea preparations and constituents thereof have demonstrated the ability to suppress inflammation, and may, therefore, be indicated in treating the symptoms of upper respiratory infections. While Echinacea demonstrated promise for this purpose in some early trials, a number of recent clinical trials have shown certain Echinacea extracts to be ineffective for treatment of upper respiratory infections. These conflicting findings may be explained at least in part by several issues with the composition of the study materials used in Echinacea research. There is still a lack of knowledge as to which specific constituents of Echinacea are appropriate markers for anti-inflammatory effects. Furthermore, among the many constituents present in complex Echinacea extracts are several that can stimulate the immune response, an activity that is likely to be undesirable when treating the symptoms of upper respiratory infections. A further complicating factor is that these immunostimulatory constituents may be produced by endophytic bacteria, bacteria that live within the Echinacea purpurea plants. With the proposed research, we seek to demonstrate ideal constituent profiles for anti-inflammatory Echinacea purpurea preparations, and to demonstrate procedures to remove constituents that stimulate the immune response. Toward this goal, we will employ a method recently developed in our research laboratory, synergy-directed fractionation, which enables the presence of specific constituents in crude extracts to be linked to biological activity. This approach can be used to identify components of complex mixtures that interact synergistically, additively, or antagonistically. As an outcome of our studies, we expect to enable more effective quality control of Echinacea purpurea extracts used for scientific research or to treat upper respiratory infections. PUBLIC HEALTH RELEVANCE: This project is relative to public health because it involves investigation of the immensely popular botanical medicine Echinacea, which is used to treat upper respiratory infections such as colds and influenza. Influenza A infections are responsible for an estimated 30,000 deaths each year in the US. With the proposed research, we seek to provide insight into the production of Echinacea preparations with enhanced efficacy for treating infections such as these.