Evaluation of athero-protective role of blue-green algae

描述（由申请人提供）：蓝绿藻（BGA）作为补充和替代医学（CAM）物质的实际使用与我们对其安全性和生物学功能的理解之间存在根本差距。长期研究目标是确定和开发CAM的天然来源，以促进最佳健康。本项目旨在评价新栽培的BGA植物Nostoc commune var. sphaeroides Kutzing （NO）的安全性和动脉粥样硬化保护特性，并阐明其保护动脉粥样硬化的分子机制。植物螺旋藻（spulina plantensis）将作为对照BGA进行比较，因为它是最常见的养殖BGA物种，已知不含藻类毒素。我们的中心假设是NO是一种安全的CAM物质，具有降胆固醇（降胆固醇）和降甘油三酯（降甘油三酯）的特性，最终延缓动脉粥样硬化的发展。在强有力的初步数据指导下，我们将通过三个具体目标来验证这一假设：1)评估BGA在体内和体外的安全性；2)评估BGA的降脂作用并确定分子机制；3)测定BGA对小鼠的抗动脉粥样硬化作用。这项工作的创新之处在于，目前还没有研究来评估BGA补充剂在体内的安全性，也没有研究来评估它们在动脉粥样硬化动物模型中的动脉粥样硬化保护功效。此外，这是第一个研究新培养的NO与目前作为膳食补充剂消费的培养SP的生物学功能的研究。由于在生产过程中可以严格控制BGA的质量和毒素污染，因此种植BGA可以避免有争议的健康问题。因此，培养的NO和SP在研究天然收获的BGA物种的生物学功能方面具有一定的价值。关于预期结果，在特定目标1-3中提出的集体工作有望通过阐明分子机制，为BGA毒性和动脉粥样硬化保护特性提供见解。这些结果将对公众健康产生重要的积极影响，为人体临床试验提供科学基础，以检验BGA作为有效可靠的CAM物质降低心血管疾病风险的功效。因此，拟议的研究非常符合NCCAM的使命，即“在严谨的科学背景下探索补充和替代治疗实践，培训CAM研究人员，并向公众和专业社区传播权威信息”。

DESCRIPTION (provided by applicant): There is a fundamental gap between the practical use of blue-green algae (BGA) as complementary and alternative medicine (CAM) substances and our understanding of their safety and biological functions. The long-term research goal is to identify and develop natural sources for CAM for promoting optimal health. The objectives of this project are to assess safety and athero-protective property of a newly cultivated BGA species Nostoc commune var. sphaeroides Kutzing (NO) and to elucidate the molecular mechanisms underlying the athero-protection. Spirulina plantensis (SP) will be used as a control BGA for comparison because it is the most common cultured BGA species that is known to be free of algal toxins. Our central hypothesis is that NO is a safe CAM substance that have hypocholesterolemic (cholesterol-lowering) and hypotriglyceridemic (triglyceride-lowering) properties, ultimately retarding the progress of atherosclerosis development. Guided by strong preliminary data, this hypothesis will be tested by pursuing three specific aims: 1) Evaluate safety of BGA in vivo and in vitro; 2) Assess lipid-lowering effects of BGA and identify molecular mechanisms; and 3) Determine anti-atherogenic roles of BGA in mice. The proposed work is innovative in that no study exists to assess safety of BGA supplementation in vivo and to mechanistically evaluate their efficacy in athero-protection using an animal model of atherosclerosis. Additionally, it is the first study that examines biological functions of newly cultivated NO in comparison with cultivated SP that is currently consumed as a dietary supplement. Cultivation of BGA can circumvent controversial health issues on BGA as quality and toxin contamination can be tightly controlled during production. In this regard, cultivated NO and SP present their worth for investigation on biological functions over naturally-harvested BGA species. With respect to expected outcomes, collective works proposed in specific aims 1-3 are expected to provide insights into BGA toxicity and athero-protective property with the elucidation of molecular mechanisms. Such results will have an important positive impact on public's health by providing scientific foundation for human clinical trials to test efficacy of BGA as effective and reliable CAM substances to reduce the risk of CVD. Therefore, the proposed research fits well to the mission of NCCAM "to explore complementary and alternative healing practices in the context of rigorous science, training CAM researchers, and disseminating authoritative information to the public and professional communities." PUBLIC HEALTH RELEVANCE: Blue-green algae products have been introduced as a dietary supplement to meet increasing public's interest in using natural products for preventive and therapeutic means for heart disease prevention. Safety and biological functions of various BGA species, however, are not properly studied. This project will assess safety and athero-protective property of newly cultivated blue-green alga Nostoc commune var. sphaeroides Kutzing together with Spirulina plantensis, which is the most common cultivated BGA in the current dietary supplement market. The project addresses an important yet under-investigated area of basic research on complementary and alternative medicine (CAM) substances that will have a positive impact on public's health by providing scientific foundation for human clinical trials to test efficacy of BGA as effective and reliable CAM substances to reduce the risk of cardiovascular disease.