Synergy in Immunomodulation by Spilanthes and Echinacea

描述（由申请人提供）：在过去的十年中，草药的使用在北美人中的流行程度急剧上升。这些补救措施是植物成分的复杂混合物，据信它们协同作用以引起生物反应。然而，很少有人知道的具体机制的协同作用，参与植物药物的生物活性。本研究的目的是探讨紫锥菊和绣线菊两种具有免疫增强活性的植物的化学成分之间的协同作用。这项研究意义重大，因为它有望提供有关两种药物免疫活性的机制信息，这两种药物在美国和欧洲被广泛用作免疫增强剂。进行这些研究的基本原理是，对金盏花和紫锥菊提取物与免疫系统相互作用的机制的理解有望有助于开发使用植物药物治疗或预防免疫相关疾病的新策略。本研究的具体目的是确定哪些成分具有免疫调节活性，并评估这些成分相互协同作用的潜力，并与紫锥菊调节免疫活性。在进行这项研究中，将测试的假设，即来自绣线菊的烷基酰胺相互之间以及与来自绣线菊和紫锥菊的其他组成基团协同作用，以调节免疫活性。这一假设已制定的基础上，初步研究表明，乙醇提取物，这些植物，这是高烷基酰胺，调节淋巴细胞和单核细胞/巨噬细胞在体外的活动。为了检验这一假设，将从紫锥菊和紫锥菊植物材料制备不同极性的植物提取物，这些植物材料已经在属和种方面得到验证。这些浸提液的化学成分将使用液相色谱-质谱联用测定。将测定浸提液和分离组分对人淋巴细胞和单核细胞/巨噬细胞系中细胞活性的影响。将从特别活性的提取物中纯化单个化合物，并将其活性与复杂提取物的活性进行比较。将使用肝素化全血对特别活性的浸提液和分离成分进行测定。将使用复杂的协同模型分析结果，以鉴定具有免疫调节潜力的特定成分组合。这些实验的大部分将在UNCG的化学系进行，其中本科生入学人数包括38%的少数民族和60%的女性，本科生密切参与研究。该提案是具有免疫学和分析化学专业知识的研究人员之间的多学科协作努力。

DESCRIPTION (provided by applicant): Over the past decade, the use of herbal remedies has skyrocketed in popularity among North Americans. Such remedies are complex mixtures of plant constituents, which are believed to interact synergistically to elicit biological responses. However, very little is known about the specific mechanisms of synergy involved in the biological activities of plant medicines. The objective of the proposed research is to investigate synergistic interactions among the chemical constituents of Echinacea and Spilanthes, two plants with purported immune-enhancing activities. This research is significant because it is expected to provide mechanistic information about the immunological activities of two medicines that are widely employed throughout the US and Europe as immune enhancers. The rationale for carrying out these studies is that an understanding of the mechanisms by which Spilanthes and Echinacea extracts interact with the immune system is expected to aid in the development of novel strategies for the use of plant medicines to treat or prevent diseases with immune related causes. The specific aims of this study are to determine which constituents from Spilanthes have immunomodulatory activity, and to assess the potential that these constituents interact synergistically with each other and with those of Echinacea to modulate immune activity. In carrying out this research, the hypothesis will be tested that alkylamides from Spilanthes interact synergistically with each other and with other constituent groups from Spilanthes and Echinacea to modulate immune activity. This hypothesis has been formulated on the basis of preliminary studies showing that ethanolic extracts of these plants, which are high in alkylamides, modulate the activity of lymphocyte and monocyte/macrophage cells in vitro. To test this hypothesis, plant extracts of varying polarity will be prepared from Echinacea purpurea and Spilanthes acmella plant material that has been verified in terms of genus and species. The chemical composition of these extracts will be determined using liquid chromatography coupled to mass spectrometry. Extracts and isolated constituents will be assayed for effects on activity of cells in human lymphocyte and monocyte/macrophage cell lines. Individual compounds will be purified from particularly active extracts, and their activities will be compared to that of complex extracts. Assays using heparinized whole blood will be performed for particularly active extracts and isolated constituents. The results will be analyzed using a sophisticated synergy model to identify specific constituents combinations with immunomodulatory potential. The bulk of these experiments will be carried out in the department of chemistry at UNCG, where undergraduate enrollment consists of 38% minority and 60% women, and undergraduate students are intimately involved in research. This proposal is a multi-disciplinary, collaborative effort between investigators with expertise in immunology and analytical chemistry.