Author

Marika Witkus

Publication Date

2014

Document Type

Honors Thesis

Department

Biological Sciences

Keywords

Nematodes, Filariasis-Prevention, Herbs-Therapeutic use, Centella asiatica., Nucleotide sequence, Genomics, Helminthiasis, Brugia, Filariasis, Drugs, RNA sequence, Helminth parasites, Macrofilaricide

Abstract

Lymphatic filariasis (LF) is a Neglected Tropical disease (NTD) that affects over 120 million people, and is the second leading cause of long-term disability worldwide (CDC 2010). LF is caused by the human parasites Wucheria bancrofti, Brugia malayi, and Brugia timori. These filarial parasites are transmitted by a mosquito vector to the human host where they nest in the lymphatic system. Once infected, the parasites can cause inflammation, lymphoedema and elephantiasis to the human host. Along with these debilitating physical afflictions, those afflicted are subject to antagonizing social stigma. Additionally, the debilitating nature of the disease has many negative socioeconomic effects on villages and countries where LF is endemic (GAELF 2004). These parasites can live for 6-8 years in the lymphatic vessels, all the while shedding new microfilariae into the blood, which can then be transmitted to new hosts thus perpetuating the cycle of transmission. In 2000 the World Health Organization (WHO) launched the Global Programme to Eliminate Lymphatic Filariasis (GPELF), who set a lofty goal of eradicating LF by 2020 using the current tools to eradicate NTDs: mass drug administration (MDA) and morbidity management. Although MDA has seen success in the past (WHO, 2012), eradication through MDA only works if there is 80% coverage within the population (Michael et al., 2004). However, due to issues of noncompliance and adverse side-effects associated with long term treatment, 80% coverage is rarely achieved in these programs (Plaisier et al., 2000). Additionally, the current drugs used in MDA mainly target the microfilariae life-stage of the parasite, which requires that the drugs be administered for 6 years to completely disrupt transmission. The inadequacies of the current drugs used to combat LF along with the potential development of resistance suggests that in order to reach the GPELF's goal and to completely eradicate the disease by 2020, new drugs that target other life-stages of the parasite are needed (Moses et al., 2010). In this study we evaluated the antifilarial activity of the medicinal plant Centella asiatica against three life-stages of the animal parasite B. pahangi, a close relative to B. malayi (Kariuki et al., 2010). When treated with an ethanol extract of C. asiatica, statistically significant mortality was observed in the adult, L3 and microfilariae (mf) life stages of the parasite. All stages of treated parasites exhibited decreased motility prior to mortality, and an irregular partial-molt morphology was observed in the L3 stage of the parasite. Additionally an expression analysis comparing treated and untreated parasites showed the differential expression of hundreds of genes. A preliminary analysis of the RNA-Seq data showed that several collagen related genes were differentially expressed 18 hours after the extract was administered. Finally, the pentacyclic triterpene asiatic acid, signature to C. asiatica, exhibited the same filariacidal activity of the crude extract on the same three life-stages of the parasite. These results along with preliminary data indicating the extract of C. asiatica has a specific toxicity all suggest that C. asiatica,and specifically asiatic acid, may be a promising candidate for antifilarial drug development.

Language

English

Comments

106 pages : illustrations (some color). Honors Project-Smith College, 2014. Includes bibliographical references (pages 102-106)

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