Project 4-Treatment of Bronchial Asthma with Borage Seed

项目4-琉璃苣籽治疗支气管哮喘

• 批准号: 6946088
• 负责人: Jonathan Peter Arm
• 金额: $ 37.55万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6946088
• 关键词: alternative medicine; angiosperms; arachidonate; asthma; clinical trial phase II; diet therapy; dietary lipid; dietary supplements; fatty acid biosynthesis; human subject; human therapy evaluation; linolenate; nutrition related tag; omega 3 fatty acid; patient oriented research; personal log /diary; plant extracts; spirometry; vegetable oils

Asthma affects about 20 million Americans, results in annual direct and indirect health care costs of approximately $8 billion, and its incidence has doubled in the last decade. Morbidity and mortality from the disease has risen proportionally and is especially prevalent among minority individuals. There is a growing demand for alternative and complementary treatments for this common disease. Leukotrienes are important in the pathogenesis of asthma, and leukotriene modifying drugs are now an established treatment for the disease. Drugs that inhibit the biosynthesis of leukotrienes are likely to more effective than the currently available drugs that antagonize a single leukotriene receptor. Dietary supplementation with gamma linolenic acid (GLA) in borage seed oil provides effective inhibition of leukotriene generation but also increases circulating free arachidonic acid (AA), which has pro-inflammatory potential. The n-3 fatty acid, eicosapentaenoic acid (EPA), prevented the conversion of GLA to AA. However, EPA is extracted from fish oil, is not well-tolerated due to its taste, and at higher doses appeared to blunt the inhibition of leukotriene biosynthesis by GLA. Stearidonic acid (SDA), is a precursor of EPA that is extracted from Echium Plantagineum; it is converted to EPA in humans and it does not have the organoleptic properties of EPA. In Specific Aim 1 we will test the hypothesis that SDA prevents the conversion of GLA to AA while maintaining effective inhibition of leukotriene biosynthesis, In Specific Aim 2 we will test the hypothesis that borage seed oil combined with echium seed oil is an effective treatment of mild to moderate persistent asthma. This Project is synergistic with Project 3 which examines the cellular and molecular anti-inflammatory mechanisms of GLA. It is synergistic with Project 2, which examines the effects and mechanisms of action of SDA in atherosclerosis. The integrated results will provide a solid scientific underpinning for future studies of these botanical oils in these and other chronic inflammatory disease.

哮喘影响约 2000 万美国人，每年造成约 80 亿美元的直接和间接医疗费用，并且其发病率在过去十年中翻了一番。该疾病的发病率和死亡率成比例上升，在少数群体中尤其普遍。对于这种常见疾病的替代和补充治疗的需求不断增长。白三烯在哮喘的发病机制中很重要，白三烯调节药物现已成为该疾病的既定治疗方法。抑制白三烯生物合成的药物可能比目前可用的拮抗单一白三烯受体的药物更有效。膳食补充剂 γ 亚麻酸 琉璃苣籽油中的 GLA（GLA）可有效抑制白三烯的生成，同时还能增加循环中具有促炎潜力的游离花生四烯酸（AA）。 n-3 脂肪酸二十碳五烯酸 (EPA) 阻止 GLA 转化为 AA。然而，EPA 是从鱼油中提取的，由于其味道而耐受性不佳，并且在较高剂量下似乎会减弱 GLA 对白三烯生物合成的抑制作用。十八碳四烯酸 (SDA) 是从车前蓝蓟中提取的 EPA 前体；它在人体中转化为 EPA，但不具有 EPA 的感官特性。在具体目标 1 中，我们将检验 SDA 阻止 GLA 转化为 AA，同时保持对白三烯生物合成的有效抑制的假设。在具体目标 2 中，我们将检验琉璃苣籽油与琉璃苣籽油结合的假设。 蓝蓟籽油可有效治疗轻度至中度持续性哮喘。该项目与研究 GLA 的细胞和分子抗炎机制的项目 3 具有协同作用。它与研究 SDA 在动脉粥样硬化中的作用和作用机制的项目 2 具有协同作用。综合结果将为这些植物油在这些疾病和其他慢性炎症性疾病中的未来研究提供坚实的科学基础。