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Bioassay Guided Isolation of Hypoglycemic Compounds from Philippine Medicinal Pla

生物测定引导下从菲律宾药用植物中分离降血糖化合物

基本信息

批准号：
8204920
负责人：
LEAH TOLOSA
金额：
$ 4.64万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE COUNTY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-02-22 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8204920
关键词：
Affect Analytical Chemistry Animals Binding Proteins Biochemistry Biodiversity Biological Biological Assay Biological Factors Biological Markers Biosensing Techniques Biosensor Blood Blood Glucose Blood specimen Buffers Caring Cell Culture Techniques Chemical Structure Chronic Disease Collaborations Complex Crude Extracts Data Data Storage and Retrieval Developed Countries Developing Countries Development Devices Diabetes Mellitus Dyes Electrical Engineering Electronics Elements Ensure Enzymes Event Fatty Acids Fermentation Filipino Fluorescence Fluorescence Spectroscopy Future Geography Glean Glucose Glutamates Glutamine Glycerol Grant Heart Diseases Herbal Medicine High Pressure Liquid Chromatography Hot Spot Housing Human Hypoglycemia Imagery Implant In Situ Indigenous Individual Kidney Diseases Lead Length Ligand Binding Maintenance Marines Measures Medicinal Plants Medicine Membrane Metabolic Methods Microdialysis Microfluidics Monitor Mus Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Pattern Pharmaceutical Preparations Pharmacologic Substance Philippines Planets Plant Components Plants Principal Investigator Property Proteins Protocols documentation Pump Pyruvate Quality Control Reading Reagent Recording of previous events Reporting Retrieval Sampling Scheme Screening procedure Series Signal Transduction Site Skin Source Surface Symptoms System Tail Techniques Testing Time Tissue Sample Traditional Medicine Universities Venipunctures Work Writing base cost design diabetic drug development experience human subject instrument interest male monitoring device multidisciplinary novel parent grant parent project prevent programs response sensor transmission process trend user-friendly wasting

项目摘要

Program Director/Principal Investigator (Last, First, Middle): Tolosa, Leah Project Description The Philippines is one of the planet's biodiversity hot spots. Of 6,000 endemic plants, it is believed that traditional doctors and herbalists use about 1,500 as medicinal plants of which only 1% has been characterized for their active components. Despite this paucity of information, in developing countries such as the Philippines where drugs imported from the developing world are beyond the purchasing power of the majority, herbal medicines remain as the main source of remedies for many ailments. Thus, the long-term objectives of this study is to definitively identify plants that are anti-diabetic based on bioassays for metabolite levels, as well as provide a novel method of quantifying efficacy of herbal medicines based on bioassay guided responses of experimental animals. The former will have an immediate impact in the availability of effective and affordable remedies for diabetes in the Philippines. The latter will provide a means of fact-based quality control of herbal medicines that at present is not always available even in the US. In order to arrive at these objectives, we propose to screen 10+ indigenous plants that have been reported to possess anti-diabetic properties. Screening will be executed at the University of the Philippines Diliman. The screening of crude extracts, fractions and isolates will be bioassay directed using a set of biosensors for glucose, glutamine and fatty acids. These biosensors are currently being developed in the Tolosa lab under project grant R01DK072465 for a device for continuous metabolite monitoring. Although the final device is not yet ready, the individual protein- based sensors can be used in an assay format to test for metabolites in blood. Thus, we propose to develop the protocols for measuring metabolite levels in Male Swiss Webster mice in response to a high glucose load. Using this bioassay protocol, we will screen and identify two plants with the most potent hypoglycemic activity from identified Philippine medicinal plants that have been folklorically reported for the treatment of diabetes. Crude extracts will be successively fractionated until the hypoglycemic constituents(s) are isolated from the two most potent Philippine medicinal plants. The chemical structures of these pure compounds will be determined by standard spectroscopic techniques. The novelty of this project is that rather than measuring a single metabolite (glucose), we will multiplex glucose, glutamine and fatty acids to see ratios and trends of these metabolites in response to a high glucose load, and then to the anti-diabetic principle(s). It should be interesting to see if patterns can be gleaned from these trends to further classify anti-diabetic compounds into groups based on their activity. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page

项目负责人/主要研究者（最后，第一，中间）：Tolosa，Leah 项目描述菲律宾是全球生物多样性热点之一。在6,000种特有植物中，传统医生和草药医生使用约1,500种药用植物，其中只有1%已被鉴定其活性成分。尽管缺乏信息，但在菲律宾等发展中国家，从发展中国家进口的药物超出了大多数人的购买力，药物仍然是治疗许多疾病的主要来源。因此，这一长期目标这项研究的目的是根据代谢物水平的生物测定，提供了一种基于生物测定引导的响应来量化草药功效的新方法，实验动物前者将对提供有效和负担得起的菲律宾糖尿病的治疗方法后者将提供一种以事实为基础的草药质量控制手段这些药物目前在美国也不总是可用的。为了实现这些目标，我们建议筛选10+已报告具有抗糖尿病特性的本土植物。筛选将在菲律宾大学Diliman进行。粗提物的筛选，将使用一组用于葡萄糖、谷氨酰胺和脂肪酸的生物传感器对馏分和分离物进行生物测定。这些生物传感器目前正在Tolosa实验室根据项目资助R 01 DK 072465进行开发，用于连续代谢物监测的装置。虽然最终的装置还没有准备好，但单个蛋白质- 基于传感器的传感器可用于测定形式以测试血液中的代谢物。因此，我们建议开发用于测量响应于高葡萄糖负荷的雄性Swiss韦伯斯特小鼠中的代谢物水平的方案。利用此生物测定方案，我们将筛选和鉴定两种具有最有效的降血糖活性的植物来自民间报道用于治疗糖尿病的已鉴定的菲律宾药用植物。将连续分级粗提物，直至从两种成分中分离出降糖成分。最有效的菲律宾药用植物。这些纯化合物的化学结构将被确定通过标准的光谱技术。这个项目的新奇在于，代谢物（葡萄糖），我们将多重葡萄糖，谷氨酰胺和脂肪酸，看看这些比例和趋势代谢物，然后是抗糖尿病成分。应当有趣的是，看看是否可以从这些趋势中收集模式，以进一步将抗糖尿病化合物分类为根据他们的活动。 PHS 398/2590（Rev. 11/07）