Project 4-Treatment of Bronchial Asthma with Borage Seed

哮喘影响了大约2000万美国人，导致每年直接和间接的医疗费用约为80亿美元，其发病率在过去十年中翻了一番。该病的发病率和死亡率成比例上升，在少数族裔个人中尤为普遍。对这种常见疾病的替代和补充治疗的需求越来越大。白三烯在哮喘的发病机制中很重要，白三烯修饰药物现在是这种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个白三烯受体的药物更有效。日粮中添加伽马亚麻酸 琉球菜籽油(GLA)可有效抑制白三烯的生成，但也可增加循环中具有促炎作用的游离花生四烯酸(AA)。N-3脂肪酸二十碳五烯酸(EPA)阻止了GLA向AA的转化。然而，EPA是从鱼油中提取的，由于其味道而不能很好地耐受，并且在更高的剂量下似乎减弱了GLA对白三烯生物合成的抑制。硬脂酸(SDA)是从车前草中提取的EPA的前体，在人体内可转化为EPA，不具有EPA的感官特性。在特定目标1中，我们将检验SDA在保持对白三烯生物合成的有效抑制的同时阻止GLA向AA转化的假说，在特定目标2中，我们将检验萝卜籽油与 灯盏花籽油是治疗轻至中度持续性哮喘的有效药物。该项目与项目3协同工作，项目3研究了GLA的细胞和分子抗炎机制。它与项目2协同作用，后者研究SDA在动脉粥样硬化中的作用和作用机制。综合结果将为未来这些植物油在这些和其他慢性炎症性疾病中的研究提供坚实的科学基础。

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.