Immune Enhancing Echinacea Bacterial Endophytes

增强免疫紫锥菊细菌内生菌

• 批准号: 8233696
• 负责人: DAVID S PASCO
• 金额: $ 36.51万
• 依托单位: UNIVERSITY OF MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8233696
• 关键词: Accounting; Agriculture; Animal Experimentation; Anti-Inflammatory Agents; Anti-inflammatory; Bacteria; Bacterial Typing; Botanicals; Cells; Clinical Research; Clinical Trials; Consumption; Data; Disease Outcome; Echinacea Preparation; Echinacea purpurea; Exhibits; Fertilization; Harvest; Health; Human; Immune; Immune Cell Activation; Immune system; Immunoglobulin A; In Vitro; Ingestion; Interferon Type II; Interleukin-6; Lipopolysaccharides; Lipoproteins; Macrophage Activation; Marketing; Methods; Mus; Nitrogen; North America; Oral; Outcome; Peritoneal Macrophages; Plant Components; Plant Roots; Plants; Polysaccharides; Preparation; Probiotics; Production; Property; Reporting; Research; Sampling; Simulate; Soil; Source; Spleen; Structure of aggregated lymphoid follicle of small intestine; System; Techniques; Therapeutic; Tissues; Tumor Necrosis Factor-alpha; Variant; Work; clinically relevant; feeding; flu; human TNF protein; immune activation; in vitro activity; in vivo; innate immune function; macrophage; meetings; novel; research clinical testing; tool

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. PUBLIC HEALTH RELEVANCE: Echinacea is one of the most widely used botanical supplements in the US. The research proposed will identify endophytic bacteria within this botanical that are the main source of bacterial components responsibe for enhancing innate immune function. 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.

描述（由申请人提供）：紫锥菊物种代表了美国草药市场中使用最广泛的免疫刺激性植物药之一。但是，疗效的临床评估遇到了不一致的结果，这些结果难以解释，因为他们使用了 多种化学不确定的制剂。此外，尽管进行了数十年的研究，但我不知道紫锥菊是对感冒和流感的主要治疗作用是免疫刺激，抗炎或两者的组合。动物研究表明，这种植物既施加治疗作用，紫chinacea烷基化代表了主要的抗炎成分。赤道酸多糖曾经被认为是该植物的免疫增强作用的造成的，并且存在于如此低的水平，并且表现出极为弱的体外先天免疫激活潜力，因此不可能在治疗上相关。我们发现，细菌成分脂多糖和Braun型脂蛋白是紫chinacea和其他免疫增强植物性植物中的体外和体内先天性免疫细胞活化剂的主要体外，而内生细菌代表了这些成分的主要来源。这两个细菌成分水平的差异是导致从北美六个主要种植者/商业供应商获得的材料的紫灰菌提取物中观察到的实质变异（约100倍）。细菌成分含量/活性的这种实质性差异可能是导致的因素 在紫锥菊临床试验中表现出的不一致的结果，因为在采用口服细菌制剂（例如益生菌）的研究中证明了与免疫相关的益处。我们的假设是，大肠杆菌内的内生细菌是LPS和Brawn型脂蛋白的主要来源，这些内生菌的数量/类型的变化是导致各种紫锥菊植物材料的免疫增强潜力的差异。我们的初步研究已经确定了大肠杆菌内的23种细菌内生物学物种，并从这些分离株中提取物很大（最高10,000倍）的能力差异很大（最多10,000倍）。 在体外激活巨噬细胞。 AIM 1将确定大肠杆菌中哪些细菌内生菌是植物材料展示的活动的主要贡献者。 AIM 2将通过口服摄入量相当于该植物材料的含量/类型的口服摄入量相等的内生细菌对小鼠的几种免疫参数的体外活性和体内作用。 AIM 3将确定影响E. purpurea的农艺因素 植物活动，并将定义导致活性变化的内生菌含量/活动的变化。实现这些目标将对紫锥菊如何影响先天的免疫系统有更深入的了解，并通过提供信息和工具来影响CAM研究，以更适当地标准化用于临床研究的紫chin虫产品。这项研究还将增加越来越多的证据，表明某些类型的细菌或细菌成分的口服消耗可能会对人类健康产生重大影响。 公共卫生相关性：紫锥菊是美国使用最广泛的植物补充剂之一。提出的研究将确定该植物学内的内生细菌，是细菌成分责任的主要来源，以增强先天免疫功能。这项研究还将增加越来越多的证据，表明某些类型的细菌或细菌成分的口服消耗可能会对人类健康产生重大影响。