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

紫锥菊、金丝桃和夏枯草具有显著的抗炎活性。这 活性可能源于1)抑制炎症因子和/或2)增强抗炎因子 炎性细胞因子。紫锥菊、金丝桃和夏枯草提取物对健康的益处可能直接 由于炎症的减少和相关症状的减少，这些潜在的 好处可能延伸到含有炎症成分的疾病。本项目将侧重于了解 在细胞和动物中，这些补充剂的抗炎和促炎活性之间的平衡 模型，以及探索它们在细胞系统中的作用机制。大体上的假说 研究表明，紫锥菊、夏枯草、紫锥菊、夏枯草提取物具有明显的抗炎活性。 金丝桃是由于相互作用的成分将免疫调节剂的复杂平衡转移到 通过调节关键的信号转导通路和随后的基因表达来抗炎。 提出了三个具体目标：1)评价紫锥菊、夏枯草和金丝桃的药效 穿孔菌原料、部位和化合物对促炎/抗炎细胞因子和 在有和没有免疫刺激的培养细胞群体中的趋化因子平衡(初级淋巴细胞 和单核/巨噬细胞，以及以下细胞系：RAW264.7巨噬细胞系，A549 人支气管上皮细胞系和MODE-K小鼠结肠上皮细胞系)。2)评估 紫锥菊、金丝桃和夏枯草在减少免疫病理和炎症反应中的作用 导致急性肺部炎症(流感)和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)评价紫锥菊和贯叶松果菊不同部位和成分对细胞的影响 调节炎症严重程度的信号通路。我们将首先使用微阵列来识别 紫锥菊和金丝桃组分改变的关键相互作用途径 3.a)。然后，我们将使用蛋白质印迹、磷酸化分析、免疫复合体激酶分析和凝胶移位。 进一步描述调节关键途径激活的潜在机制的技术 (目标3.b)。这些研究将加深我们对松果菊属、金丝桃属和夏枯草属的了解 有助于这些属的抗炎活性的成分，并确定这些属是否， 可能对治疗肺和结肠的炎症过程有价值。此外，建议的 研究将评估这些益处背后的细胞机制，重点放在 已被证明在调节促炎和抗炎过程中起着中心作用。

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.