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功能的理解之间存在根本性差距。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。本项目的目的是评估安全性和动脉粥样硬化保护性能的一个新栽培的BGA物种念珠藻普通变种。sphaeroides Kutzing（NO）的表达，阐明其抗动脉粥样硬化的分子机制。螺旋藻（SP）将用作对照BGA进行比较，因为它是已知不含藻毒素的最常见的培养BGA物种。我们的中心假设是NO是一种安全的CAM物质，具有降低胆固醇和降低胆固醇的特性，最终延缓动脉粥样硬化的发展。在强有力的初步数据的指导下，将通过追求三个特定目标来检验这一假设：1）评价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）确定BGA在小鼠中的抗动脉粥样硬化作用。所提出的工作是创新的，因为没有研究存在评估BGA补充剂在体内的安全性和使用动脉粥样硬化动物模型机械地评估其在动脉粥样硬化保护中的功效。此外，这是第一项研究，研究了新培养的NO与目前作为膳食补充剂消费的培养SP的生物学功能。BGA的培养可以避免BGA上有争议的健康问题，因为在生产过程中可以严格控制质量和毒素污染。在这方面，栽培NO和SP提出了他们的价值的生物学功能的研究比自然收获的BGA物种。关于预期结果，具体目标1-3中提出的集体工作预计将提供对BGA毒性和动脉粥样硬化保护特性的见解，并阐明分子机制。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依据，以测试BGA作为有效和可靠的CAM物质降低CVD风险的功效。因此，拟议的研究非常适合NCCAM的使命“在严格的科学背景下探索补充和替代的治疗方法，培训CAM研究人员，并向公众和专业团体传播权威信息。" 公共卫生相关性：蓝绿藻产品已被引入作为膳食补充剂，以满足公众对使用天然产品预防和治疗心脏病的兴趣。然而，各种BGA物种的安全性和生物学功能尚未得到适当的研究。本项目将评估新栽培的蓝绿色普通念珠藻的安全性和抗动脉粥样硬化性能。sphaeroides Kutzing与螺旋藻（Spirulina plantensis）一起，螺旋藻是目前膳食补充剂市场上最常见的栽培BGA。该项目涉及补充和替代医学（CAM）物质基础研究的一个重要但尚未得到充分研究的领域，该领域将通过为人体临床试验提供科学基础来测试BGA作为有效和可靠的CAM物质的功效，从而对公众健康产生积极影响，以降低心血管疾病的风险。

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.