Potential of the bitter melon Momordica charantia as a source of anthelmintics

摘要：寄生性线虫(PN)感染仍然是全球人类健康的主要威胁。超过1.5 10亿人感染PNS，儿童、孕妇和老年人尤其容易感染 由线虫感染引起的发病率。控制策略仅限于定期驱除受感染的蠕虫 个人，这受到快速的再感染率和不可避免的抗药性蠕虫发展的限制 人口。目前还没有针对人类PN感染的疫苗。因此，有一个明确的和 迫切需要治疗PN感染的新药，以防止出现耐药菌株。美国国家安全局 钩虫可以说是感染人类的最重要的因素，因为它们贪婪地吸血活动。 疾病控制和预防中心估计，钩虫目前感染了5.76-7.4亿人 世界各地的人们。感染可能导致贫血和蛋白质缺乏，导致胃肠道健康 普遍存在的问题会阻碍儿童的成长和认知发展。苦瓜苦瓜 轮虫在钩虫流行的地区广泛种植，并已被用作传统药物 用于发展中国家的寄生虫感染和其他疾病。苦瓜水提物(MCE) 已证明能抑制感染钩虫幼虫(L3)的摄食，并能杀死成虫和L4钩虫。 以及其他几种线虫。生物活性物质的化学鉴定与表征 成分(S)可能导致开发一种治疗钩虫和其他PN感染的药物。在这里，我们建议 用钩虫死亡率法分离沙门氏菌驱虫活性成分(S) 用丝状钩口线虫筛选组分。在目标1中，我们将使用天然产物化学来分离 从植物材料的其余部分提取有效成分(S)和鉴定有效驱虫剂的生物测定 (S)在MCE内部。在目标2中，我们将确定单独的驱虫剂是否能成功治疗 钩虫体内感染。确定MCE中负责植物健康的活性成分 显著的驱虫活性并证实其体内活性可能导致开发一种新的 驱虫剂，用于治疗钩虫和其他PNS。

Abstract: Parasitic nematode (PN) infections remain a major threat to human health globally. More than 1.5 billion people are infected with PNs, with children, pregnant women, and the elderly especially susceptible to morbidity from nematode infection. Control strategies are restricted to periodic de-worming of infected individuals, which is limited by rapid re-infection rates and the inevitable development of drug resistant worm populations. There are currently no vaccines available for human PN infections. Therefore, there is a clear and pressing need for new drugs to treat PN infections to forestall the emergence of resistant isolates. Of the PNs infecting humans, hookworms are arguably the most important due to their voracious blood feeding activities. The Center for Disease Control and Prevention estimates that hookworm currently infects 576-740 million people worldwide. Infection may cause anemia and protein deficiency, causing gastrointestinal health problems generally and retarded growth and cognitive development in children. The bitter melon Momordica charantia is widely grown in areas where hookworm is endemic, and has been used as a traditional medicine for parasitic infections and other disease in developing countries. Aqueous extracts of M. charantia (MCE) have been shown to inhibit feeding of infective hookworm larvae (L3) and to kill adult and L4 hookworm in vitro, as well as several other nematodes. Chemical identification and characterization of the biologically active component(s) may lead to development of a drug to treat hookworm and other PN infections. Here we propose to isolate the active anthelmintic compound(s) from M. charantia using mortality of the hookworm Ancylostoma ceylanicum to screen fractions. In Aim 1, we will use natural product chemistry to separate the active component(s) from the rest of the plant material and a bioassay to identify the active anthelmintic compund(s) within MCE. In Aim 2, we will determine if the isolated anthelmintic can successfully treat hookworm infections in vivo. Identifying the active components of MCE that are responsible for the plant’s remarkable anthelmintic activity and confirming its in vivo activity may lead to the development of a new anthelmintic for the treatment of hookworm and other PNs.