Immune Enhancing Echinacea Bacterial Endophytes

描述（由申请方提供）：紫锥菊属是美国草药市场上使用最广泛的免疫刺激植物药之一。然而，疗效的临床评价遇到了难以解释的不一致结果，因为他们使用了 各种化学性质不明确的制剂此外，尽管经过几十年的研究，我不知道紫锥菊对感冒和流感的主要治疗作用是免疫刺激，抗炎还是两者兼而有之。动物研究表明，这种植物发挥治疗作用和紫锥菊烷基酰胺代表的主要抗炎成分。紫锥菊多糖，曾经被认为是该植物的免疫增强作用的原因，以如此低的水平存在，并表现出极弱的体外先天免疫激活潜力，因此不太可能是治疗相关的。我们已经发现，细菌组分脂多糖和Braun型脂蛋白是紫锥菊和其他免疫增强植物中的主要体外和体内先天免疫细胞激活剂，并且那些内生细菌代表这些组分的主要来源。这两种细菌组分水平的差异是导致在E.从北美六个主要种植者/商业供应商获得的材料的purpurea提取物。细菌组分含量/活性的这种实质性变化可能是促成 紫锥菊临床试验中表现出的不一致结果，因为免疫相关的益处已经在采用口服给药的细菌制剂如益生菌的研究中得到证实。我们的假设是，E.紫锥菊属植物是LPS和布朗型脂蛋白的主要来源，并且这些内生菌的量/类型的变化是造成不同紫锥菊属植物材料的免疫增强潜力差异的原因。我们的初步研究已经确定了23种细菌内生菌在E。purpurea和提取物从这些分离物的能力差异很大（高达10，000倍）， 在体外激活巨噬细胞。目的1将确定哪些细菌内生菌在E.紫花苜蓿是植物材料所表现出的活性的主要贡献者。目的二是确定E.紫花苜蓿对小鼠几种免疫参数的影响可以通过口服与这种植物材料中发现的数量/类型相当的内生细菌来模拟。目的3确定影响E. purpurea 植物活性，并将定义负责活性变化的内生菌含量/活性的变化。实现这些目标将使人们更好地了解紫锥菊如何影响先天免疫系统，并通过提供信息和工具来更适当地标准化紫锥菊产品以用于临床研究，从而影响CAM研究。这项研究还将增加越来越多的证据，表明口服某些类型的细菌或细菌成分会对人类健康产生重大影响。

DESCRIPTION (provided by applicant): Echinacea species represent one of the most widely used immunostimulatory botanicals in the US herbal market. However, clinical evaluation of efficacy has met with inconsistent results that are difficult to interpret because they have used a wide variety of chemically ill-defined preparations. In addition, despite decades of research, it i not known if Echinacea's main therapeutic action on colds and flu is immunostimulatory, anti-inflammatory or a combination of both. Animal research indicates that this botanical exerts both therapeutic actions and Echinacea alkylamides represent the major anti-inflammatory component. Echinacea polysaccharides, once thought to be responsible for the immune enhancing action of this plant, are present at such low levels and exhibit extremely weak in vitro innate immune activation potential and thus are not likely to be therapeutically relevant. We have found that the bacterial components lipopolysaccharides and Braun-type lipoproteins are major in vitro and in vivo innate immune cell activators within Echinacea and other immune enhancing botanicals and those endophytic bacteria represent the principal source of these components. Differences in the levels of these two bacterial components are responsible for the substantial variation observed (~100-fold) in innate immune cell activation from E. purpurea extracts of material obtained from six major growers/commercial suppliers in North America. This substantial variability in bacterial component content/activity could be a factor contributing to the inconsistent outcomes exhibited in Echinacea clinical trials since immune related benefits have been demonstrated in studies employing orally administered bacterial preparations such as probiotics. Our hypothesis is that endophytic bacteria within E. purpurea are a major source of LPS and Brawn type lipoproteins and variation in the amount/type of these endophytes are responsible for differences in the immune enhancing potential of diverse Echinacea plant material. Our preliminary studies have identified 23 bacterial endophytic species within E. purpurea and extracts from these isolates varied substantially (up to 10,000-fold) in their ability to activate macrophages in vitro. Aim 1 will identify which bacterial endophytes within E. purpurea are principal contributors to the activity exhibited by the plant material. Aim 2 will determine if the in vitro activity and in vivo action of E. purpurea on several immune parameters in mice can be mimicked by the oral ingestion of endophytic bacteria equivalent in amount/type to that found in this plant material. Aim 3 will identify agronomic factors influencing E. purpurea plant activity and will define shifts in endophyte content/activity responsible for activity change. Accomplishing these objectives will provide a greater understanding of how Echinacea influences the innate immune system and will impact CAM research by providing the information and tools to more appropriately standardize Echinacea products for use in clinical studies. This research will also add to the growing body of evidence that indicates that the oral consumption of certain types of bacteria or bacterial components can have a major impact on human health.