Bioassay Methods for Standardization of Immune Enhancing Dietary Supplements

免疫增强膳食补充剂标准化的生物测定方法

• 批准号: 8921680
• 负责人: Mahmoud A ElSohly
• 金额: $ 19.24万
• 依托单位: PSI (PHYTOCHEMICAL SERVICES, INC.)
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8921680
• 关键词: Address; Aloe vera plant; Anti-Inflammatory Agents; Anti-inflammatory; Bacteria; Biological; Biological Assay; Biological Factors; Botanicals; Chemicals; Clinical Trials; Detection; Development; Exhibits; Health; Health Benefit; Human; Immune; Industry; Interleukin-1; Macrophage Activation; Manufacturer Name; Measures; Methods; Mississippi; Molecular; Molecular Weight; Mus; Outcome; Peritoneal Macrophages; Pharmacologic Substance; Phase; Phytochemical; Polysaccharides; Preparation; Process; Production; Property; Quality Control; Reference Standards; Research; Research Personnel; Sampling; Services; Small Business Technology Transfer Research; Solvents; Source; Spirulina preparation; Standardization; System; Techniques; Technology; Testing; Therapeutic; Tumor Necrosis Factor-alpha; Universities; Variant; Work; base; biological standardization; chemical standardization; cytokine; dietary supplements; human TNF protein; improved; in vitro Assay; in vitro Bioassay; in vivo; interest; macrophage; public health relevance; success

 DESCRIPTION (provided by applicant): Clinical trials testing the potential health benefits of immune enhancing dietary supplements have produced inconsistent results. A major problem contributing to these inconsistent outcomes is that these studies have used a wide variety of poorly characterized products. Attempts to solve this product quality control problem using chemical standardization methods has had limited success because physiochemical properties cannot fully predict the biological potency of the high molecular weight substances that are typically responsible for the immune enhancing effects of these supplements. The objective of this application is to develop services for standardizing the potency of a broad range of immune enhancing dietary supplements based on biological activity using technology developed by the University of Mississippi (UM). University of Mississippi has set-up a battery of in vitro assay systems capable of detecting different high molecular weight components that activate macrophages. The components detected by these bioassays are relevant for standardization because they impact immune parameters in vivo and are thought to be responsible for the therapeutic action of these products. The University of Mississippi has also developed methods to remove nuisance compounds that interfere with the detection of macrophage activation as well as methods for the preparation of extracts based on solvent-specific extractability of the active components. The Specific Aims are as follows: 1. Prepare extracts from 8 different immune enhancing dietary supplements of commercial interest. Botanical raw material will be processed to remove nuisance compounds that interfere with detection of activity followed by preparation of three different types of extracts that concentrate different classes of active compounds. 2. Identify the in vitro bioassays to be used for biological standardization of each dietary supplement. Extracts prepared in Aim 1 will be assessed in a battery of three in vitro bioassays that detect potency of macrophage activation exhibited by the following activators: bioassay 1 (components from endophytic bacteria), bioassay 2 (polysaccharides) and bioassay 3 (inflammasome activators). Results will determine the appropriate bioassay and type of extract to be used for standardization of each dietary supplement. 3. Develop biological reference standards. Reference standards will be developed for each supplement that can be used to determine the potency of unknown samples and to define accuracy of each bioassay. Accomplishing these objectives will provide a valuable technology to quantitate the potency of immune enhancing dietary supplements so that these products can be manufactured to exhibit consistent therapeutic properties for consumers and for use in clinical trials. It is envisioned tht Phase II will define additional bioassay parameters, further establish the therapeutic relevance of the bioassay endpoints, and begin to offer services to standardize products based on bioactivity. This STTR application represents a collaborative effort between Phytochemical Services, Inc. (PSI) and the University of Mississippi National Center for Natural Products Research.

 描述（由适用提供）：测试免疫饮食补充剂的潜在健康益处的临床试验产生了不一致的结果。导致这些不一致结果的一个主要问题是，这些研究使用了各种各样的特征性较差的产品。尝试使用化学标准化方法解决此产品质量控制问题的尝试取得了有限的成功，因为理化特性无法完全预测通常负责这些补充剂免疫促进作用的高分子量物质的生物学效力。该应用程序的目的是开发服务，以使用密西西比大学（UM）开发的技术基于生物学活动的广泛免疫饮食补充剂的效力。密西西比大学建立了一组体外评估系统，能够检测激活巨噬细胞的不同高分子量成分。这些生物测定检测到的组件与标准化有关，因为它们会影响体内免疫参数，并被认为是这些产品的治疗作用负责。密西西比大学还开发了去除干扰巨噬细胞激活的滋扰化合物的方法，以及基于活性成分的溶剂特异性提取性制备提取物的方法。具体目的如下：1。从8种不同的免疫饮食补充剂的商业兴趣的摘录中提取。将处理植物原料以去除干扰活性检测的滋扰化合物，然后制备三种不同类型的提取物，这些提取物浓缩了不同类别的活性化合物。 2。确定用于每种饮食补充剂的生物标准化的体外生物测定。在AIM 1中制备的提取物将在三个体外生物测定的电池中进行评估，该电池可检测以下激活剂表现出的巨噬细胞激活的效力：生物测定1（内生细菌的成分），生物测定2（多糖）和生物测定3（炎症体激活物）。结果将确定适当的生物测定和提取物类型，用于标准化每种饮食补充剂。 3。制定生物学参考标准。将为每种补充剂开发参考标准，可用于确定未知样品的效力并定义每个生物测定的准确性。实现这些目标将提供一项有价值的技术，以量化免疫增强饮食补充剂的效力，以便可以制造这些产品以表现出一致的消费者治疗特性，并用于临床试验。可以预见，第二阶段将定义其他生物测定参数，进一步建立生物测定端点的治疗相关性，并开始提供基于生物活性的产品标准化产品的服务。该STTR应用程序代表了植物化学服务公司（PSI）和密西西比大学国家天然产品研究中心之间的合作努力。