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

紫锥花、金丝桃的抗炎活性

• 批准号: 7293895
• 负责人: DIANE F BIRTH
• 金额: $ 27.64万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7293895
• 关键词: A549; Accounting; Acute; Andro-Diane; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Antigen-Antibody Complex; Antigens; Back; CD8B1 gene; Cannabinoids; Cell Line; Cells; Chemicals; Colitis; Colon; Complex; Critical Pathways; Cultured Cells; Disease; Disease Outcome; Echinacea (Asteraceae); Echinacea Preparation; Electrophoretic Mobility Shift Assay; Environment; Epithelial Cells; Equilibrium; Gene Expression; Genes; Genus Cola; Health Benefit; Human; Hypericum; Hypericum perforatum; Immune; Immune Cell Activation; Immune system; Infection; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Influenza; Interleukin-10; Investigation; Laboratories; Lesion; Leukocytes; Literature; Lung; Lung Lavage Fluid; Lymphocyte; MAPK14 gene; Mediating; Modeling; Mus; Pathway interactions; Phosphorylation; Phosphotransferases; Plant Extracts; Pneumonia; Population; Principal Investigator; Process; Production; Property; Prunella (angiosperm); Resolution; Respiratory Tract Infections; Role; Severities; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Site; Sodium Dextran Sulfate; Symptoms; System; Technology; Viral; Viral Load result; Virus Diseases; Western Blotting; cell type; chemokine; cytokine; human MAPK14 protein; immunopathology; in vivo; killings; knock-down; macrophage; mitogen-activated protein kinase p38; monocyte; mouse model; programs; respiratory; A549; Accounting; Acute; Andro-Diane; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Antigen-Antibody Complex; Antigens; Back; CD8B1 gene; Cannabinoids; Cell Line; Cells; Chemicals; Colitis; Colon; Complex; Critical Pathways; Cultured Cells; Disease; Disease Outcome; Echinacea (Asteraceae); Echinacea Preparation; Electrophoretic Mobility Shift Assay; Environment; Epithelial Cells; Equilibrium; Gene Expression; Genes; Genus Cola; Health Benefit; Human; Hypericum; Hypericum perforatum; Immune; Immune Cell Activation; Immune system; Infection; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Influenza; Interleukin-10; Investigation; Laboratories; Lesion; Leukocytes; Literature; Lung; Lung Lavage Fluid; Lymphocyte; MAPK14 gene; Mediating; Modeling; Mus; Pathway interactions; Phosphorylation; Phosphotransferases; Plant Extracts; Pneumonia; Population; Principal Investigator; Process; Production; Property; Prunella (angiosperm); Resolution; Respiratory Tract Infections; Role; Severities; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Site; Sodium Dextran Sulfate; Symptoms; System; Technology; Viral; Viral Load result; Virus Diseases; Western Blotting; cell type; chemokine; cytokine; human MAPK14 protein; immunopathology; in vivo; killings; knock-down; macrophage; mitogen-activated protein kinase p38; monocyte; mouse model; programs; respiratory

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.

已经发现紫锥菊，甲状腺赛和prunella具有明显的抗炎活性。这 活性可能是由1）抑制炎症因子和/或，2）抗抗抗素的增强 炎症细胞因子。紫锥菊，金丝桃和蛋白酶提取物的健康益处可能直接 炎症减少和症状的减少以及这些潜力导致 益处可能扩展到具有炎症成分的疾病。该项目将集中于理解 这些补充剂的抗炎活性和动物的抗炎活性之间的平衡 模型，以及探测其在细胞系统中的作用机理。基本的总体假设 研究是从紫锥菊，蛋白酶或 Hypericum是由于相互作用的成分，这些成分将免疫调节剂的复杂平衡转移到 通过调节关键信号转导途径和随后的基因表达，抗炎谱。 提出了三个具体目的：1）评估紫锥菊，普鲁纳氏菌和hypericum的影响 促炎 /抗炎细胞因子的详细剂，分数和化合物 趋化因子平衡，在有或没有免疫刺激的培养细胞群中（原发性淋巴细胞） 和单核细胞/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鼠结肠上皮细胞系）。 2）评估 紫锥菊，金丝桃木和prunella在确定的免疫病理学和炎症中的作用 呼吸道病毒感染的动物模型，导致急性肺部炎症（流感）和 炎症性疾病（硫酸葡萄糖钠[DSS]诱导的结肠炎模型的炎症性肠病模型）。 3）评估紫锥菊和厚型螺旋杆菌对细胞的影响和成分的影响 在炎症严重程度下调节的信号通路。我们最初将使用MicroArraysto标识 由紫锥菊和金丝桃木的成分和分数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，免疫复合激酶测定和凝胶移位 进一步描述调节关键途径激活的基本机制的技术 （AIM 3.B）。拟议的研究将进一步理解紫锥菊，甲状腺赛和prunella 有助于这些属的抗炎活性的成分，并确定这些属是否是否 在治疗肺和结肠中的炎症过程中可能很有价值。此外，提议 研究将评估这些益处的细胞机制，重点是信号通路 已显示在调节促和抗炎过程中是核心。