ANTI-INFLAMMATORY ACTIVITY OF ECHINACEA, HYPERICUM & PRUNELLA SPECIES/BIRT, DIANE

紫锥花属、金丝桃属和夏枯草属已被发现具有明显的抗炎活性。这 活性可由1）抑制炎性因子和/或，2）增强抗- 炎性细胞因子紫锥菊、金丝桃和夏枯草提取物的健康益处可以直接 结果是炎症减少和相关症状减少，这些潜在的 益处可延伸至具有炎性成分的疾病。本项目将重点关注理解 这些补充剂在细胞和动物中的抗炎和促炎活性之间的平衡 模型，并探讨其在细胞系统中的作用机制。根据一个总体假设， 研究表明，从紫锥菊、夏枯草或 金丝桃是由于相互作用的成分，使免疫调节剂的复杂平衡向免疫调节剂转移。 通过调节关键信号传导途径和随后的基因表达来发挥抗炎作用。 提出了三个具体的目的：1）评估紫锥菊，夏枯草和金丝桃的作用 穿孔草种子、级分和化合物对促炎/抗炎细胞因子和 在有和没有免疫刺激的培养细胞群中的趋化因子平衡（原代淋巴细胞 RAW264.7巨噬细胞系，A549巨噬细胞系， 人支气管上皮细胞系和MODE-K鼠结肠上皮细胞系）。2)评估 紫锥菊、金丝桃和夏枯草在最大限度地减少建立的免疫病理学和炎症中的作用 导致急性肺部炎症（流感）的呼吸道病毒感染的动物模型， 炎症性疾病（葡聚糖硫酸钠[DSS]诱导的炎症性肠病结肠炎模型）。 3)评价紫锥菊和H.细胞上的穿孔种质 调节炎症严重程度的信号通路。We will initial初始use micro微阵列to identify识别 紫锥菊和金丝桃属的组分和级分改变的关键相互作用途径（Aim 3.a）。然后我们将使用蛋白质印迹，磷酸化分析，免疫复合物激酶测定和凝胶转移， 技术，以进一步阐明调节关键途径激活的潜在机制 (Aim 3.b）。这些研究将进一步加深我们对紫锥菊属、金丝桃属和夏枯草属植物的认识 有助于这些属的抗炎活性并决定这些属， 可能在治疗肺和结肠的炎症过程中有价值。此外，拟议的 研究将评估这些益处背后的细胞机制，重点是信号通路， 已被证明是调节促炎和抗炎过程的中心。

Echinacea, Hypericum and Prunella have been found to have appreciable anti-inflammatory activity. This activity may result from 1) an inhibition of inflammatory factors and/or, 2) an enhancement of anti- inflammatory cytokines. The health benefits of Echinacea, Hypericum, and Prunella extracts may directly result from a reduction in inflammation and an associated reduction in symptoms, and these potential benefits may extend to diseases with an inflammatory component. This Project will focus on understanding the balance between the anti- and pro-inflammatory activities of these supplements, both in cell and animal models, and on probing their mechanisms of action in cell systems. The overarching hypothesis under investigation is that the anti-inflammatory activity of fractions prepared from Echinacea, Prunella, or Hypericum is due to interacting constituents that shift the complex balance of immune-modulators toward an anti-inflammatory profile by modulating key signal transduction pathways and subsequent gene expression. Three Specific Aims are proposed: 1) Assessing the effects of Echinacea, Prunella, and Hypericum perforatum accessions, fractions and compounds on pro-inflammatory / anti-inflammatory cytokine and chemokine balance, in cultured cell populations with and without immune stimulation (primary lymphocytes and monocyte/macrophages, and the following cell lines: the RAW264.7 macrophage cell line, the A549 human bronchial epithelial cell line, and the MODE-K murine colonic epithelial cell line). 2) Assessing the role of Echinacea, Hypericum and Prunella in minimizing immunopathology and inflammation in established animal models of respiratory viral infection that result in acute pulmonary inflammation (influenza) and inflammatory disease (dextran sulfate sodium [DSS]-induced colitis model of inflammatory bowel disease). 3) Evaluating the effects of fractions and constituents of Echinacea and H. perforatum accessions on cellular signaling pathways that regulate in the severity of inflammation. We will initially use microarraysto identify the key interacting pathways that are altered by constituents and fractions of Echinacea and Hypericum (Aim 3.a). We will then use western blots, phosphorylation analysis, immune complex kinase assays, and gel shift technologies to further delineate the underlying mechanisms that regulate the activation of the key pathways (Aim 3.b). The proposed studies will further our understanding of Echinacea, Hypericum and Prunella constituents that contribute to the anti-inflammatory activity of these genera and determine if these genera, may be of value in treating inflammatory processes in the lung and colon. Furthermore, the proposed studies will assess the cellular mechanisms underlying these benefits, focusing on signaling pathways that have been shown to be central in regulating pro- and anti-inflammatory processes.