Unraveling Immunostimulatory and Immunosuppressive Effects of Echinacea purpurea

描述（由申请人提供）：疾病控制中心报告，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，这种疾病每年折磨成年人2 - 4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证明具有抑制炎症的能力，因此可用于治疗上呼吸道感染的症状。虽然紫锥菊在一些早期的试验中显示出对这一目的的希望，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可以部分解释为在紫锥菊研究中使用的研究材料组成的几个问题。关于紫锥菊的哪些特定成分是抗炎作用的适当标记物，仍然缺乏知识。此外，在复杂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，这种活性在治疗上呼吸道感染症状时可能是不可取的。一个更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，这些细菌生活在紫锥菊植物中。通过提出的研究，我们试图证明抗炎紫锥菊制剂的理想成分，并证明去除刺激免疫反应成分的程序。为了实现这一目标，我们将采用我们研究实验室最近开发的一种方法，协同定向分馏，该方法可以将粗提取物中特定成分的存在与生物活性联系起来。该方法可用于识别复杂混合物中协同作用、加和作用或拮抗作用的组分。通过本研究的结果，我们希望能够更有效地控制用于科学研究或治疗上呼吸道感染的紫锥菊提取物的质量。

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.