Monday, May 13, 2024
5/13/2024
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.
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