Project 4-Treatment of Bronchial Asthma with Borage Seed

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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.