Anthelmintic Activity of Plant Natural Products Against the Hookworm Ancylostoma

植物天然产物对钩虫钩虫的驱虫活性

基本信息

批准号：
8794969
负责人：
Gil Belofsky
金额：
$ 36.11万
依托单位：
CENTRAL WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-01-01 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8794969
关键词：
Adult Albendazole Ancylostoma (genus)Anemia Animal Diseases Animal Model Anthelmintics Antibodies Area Benzimidazoles Biological Assay Biological Factors Blood Body Weight decreased Cell Proliferation Cells Child Chronic Clinical Cognitive Collection Communicable Diseases Country Crude Extracts Culture Techniques Data Development Disease Drug resistance Drug usage Environment Evaluation Exhibits Farming environment Fetus Future Goals Growth HIV Hamsters Health Hookworm Infections Hookworms Hour Human Immune Impairment Incubated Intestinal parasite Intestines Iron deficiency anemia Laboratories Lead Livestock Low Birth Weight Infant Malaria Malnutrition Mentors Mesocricetus auratus Methods Milk Modeling Mothers Multi-Drug Resistance Nematoda Nematode infections Output Parasites Pharmaceutical Preparations Plant Extracts Plants Population Population Sizes Pregnancy Production Protocols documentation Public Health Reporting Research Research Personnel Resistance Resistance development Resources S-Phase Fraction Science Soil Source Students Testing Therapeutic Translations Tuberculosis Vaccines Weight Gain Work adverse outcome base benzimidazole cell motility design egg experience feeding fight against human disease in vivo instrumentation marine organism meetings microorganism mortality neonate novel therapeutics public health relevance research study screening success tool

项目摘要

DESCRIPTION (provided by applicant): Hookworms, blood feeding intestinal parasites, remain a major health burden with approximately a billion people infected in tropical and subtropical regions of the world. In these geographical areas, they are a major contributor to iron-deficiency anemia, weight loss, stunted growth and malnutrition. Control strategies have relied on mass treatment with benzimidazole drugs. However, recent reports have described the resistance of hookworms and other soil-transmitted nematodes to these drugs. Consequently, there is an urgent need to develop alternative control tools such as vaccines and novel therapeutics. Our proposal aims at identifying and characterizing plant compounds with activity against the hookworm Ancylostoma ceylanicum, one of the species causing the human disease. Two plant candidate species tested during our preliminary studies, namely Dalea ornata and Oemlaria cerasiformis, showed anthelminthic activity (mortality and/or reduced motility) in crude extracts and enriched fractions. Associated worm mortality rates ranged from 25% at 24 hours to 100% at 120 hours, after incubating worms with the test compounds. Accordingly, the following hypotheses will be tested: 1) Plants represent a relatively untapped source of potentially effective anthelminthic molecules. 2) Plant extracts, enriched chromatographic fractions, and purified components are active ex vivo and in vivo against adult hookworms. The planned studies will isolate active component(s) of D. ornata and O. cerasiformis and assess their activity using both ex vivo and in vivo protocols developed in our lab. Evaluation of the effects of active component(s) on the hookworm infection will be evaluated using clinical, parasitological and immunological parameters such as weight gain, anemia, egg output, worm burden, immune cell proliferation indices, immune cell population sizes, and hookworm-specific antibody levels.

描述（由申请人提供）：钩虫，血液喂食肠道寄生虫仍然是一个重大的健康负担，世界上有大约十亿人感染了世界的热带和亚热带地区。在这些地理区域，它们是导致铁缺陷贫血，体重减轻，发育迟缓和营养不良的主要贡献者。控制策略依赖于苯咪唑药物的大规模治疗。但是，最近的报道描述了钩虫和其他土壤传播的线虫对这些药物的抗性。因此，迫切需要开发替代控制工具，例如疫苗和新型治疗剂。我们的建议旨在鉴定和表征植物化合物，其活性针对钩虫ceylanicum，这是引起人类疾病的物种之一。在我们的初步研究中测试的两种植物候选物种，即Dalea ornata和oemlaria cerasiformis，在粗提物和富集的分数中显示出驱虫活性（死亡率和/或降低运动性）。与测试化合物一起孵育蠕虫后，相关的蠕虫死亡率范围从24小时时24小时到120小时的100％不等。因此，将测试以下假设：1）植物代表了相对尚未开发的潜在有效驱虫分子的来源。 2）植物提取物，富集的色谱级分和纯化的成分是活体活体和体内针对成人钩虫的。计划的研究将隔离D. ornata和o。cerasiformis的活性成分，并使用在我们实验室中开发的离体和体内方案来评估其活性。将使用临床，寄生学和免疫学参数（例如体重增加，贫血，卵子输出，蠕虫负担，免疫细胞增殖指数，免疫细胞种群和钩虫特异性抗体水平）评估活性成分对钩虫感染的影响。