Abstract
Neglected tropical diseases are major health hazards in developing countries. Annually, up to 30 million people are affected by either Chagas disease, African trypansomiasis or leishmaniasis, and more than 200 million by malaria. Most of the currently available drugs have drawbacks in terms of toxicity, limited oral availability, development of resistance, or non-affordability. Tropical plants of the arid zones are a treasure chest for the discovery of bioactive secondary metabolites. This study aims to compile Sudanese medicinal plants, validate their antiprotozoal activities, and identify active molecules. We have performed a survey of medicinal plants of Sudan and selected 62 that are being used in Sudanese traditional medicine. From these, we collected materials such as leaves, stem, bark, or fruit. The plant materials were extracted in 70% ethanol and further fractionated by liquid-liquid partitioning using solvents of increasing polarity. This resulted in a library of 235 fractions. The library was tested in vitro against Plasmodium falciparum (erythrocytic stages), Trypanosoma brucei rhodesiense (bloodstream forms), Trypanosoma cruzi (intracellular amastigotes), and Leishmania donovani (axenic amastigotes). Active fractions were also tested for cytotoxicity. Of the 235 fractions, 125 showed growth inhibitory activity >80% at 10 μg/ml, and >50% at 2 μg/ml against at least one of the protozoan parasites. Plasmodium falciparum was the most sensitive of the parasites, followed by T. b. rhodesiense and L. donovani. Only few hits were identified for T. cruzi, and these were not selective. Contrary to expectation based on phylogeny, but in agreement with previous results, a large number of extracts displayed mutual activity against T. brucei and P. falciparum. HPLC-based activity profiling for selected active extracts was performed to identify the bioactive principles. Active compounds identified by dereplication were guieranone A from Guiera senegalensis J.F.Gmel.; pseudosemiglabrin from Tephrosia apollinea (Delile) DC; ellagic acid and quercetin from Terminalia leiocarpa (DC.) Baill.; and catechin, ethyl gallate, and epicatechin gallate from Vachellia nilotica (L.) P.J.H.Hurter & Mabb. Also the extracts of Croton gratissimus var. gratissimus and Cuscuta hyalina Roth ex Schult. exhibited promising antitrypanosomatid activity. This assessment provides a comprehensive overview of Sudanese medicinal plants and supports the notion that they are a potential source of bioactive molecules against protozoan parasites.
Highlights
Infections by protozoan parasites remain to be among the most devastating causes of mortality in the tropics
The trypanosomatids are a large family of flagellated protozoa, some of which cause neglected tropical diseases of high public health relevance and socio-economic impact (WHO, n.d.; Filardy et al, 2018)
The apicomplexan parasite Plasmodium falciparum is the causative agent of malaria tropica, the most dangerous form of malaria, which—despite the successes by various international bodies and philanthropic organizations—still claims an annual death toll of 435,000 (World Health Organisation, 2018)
Summary
Infections by protozoan parasites remain to be among the most devastating causes of mortality in the tropics. The trypanosomatids are a large family of flagellated protozoa, some of which cause neglected tropical diseases of high public health relevance and socio-economic impact (WHO, n.d.; Filardy et al, 2018). The apicomplexan parasite Plasmodium falciparum is the causative agent of malaria tropica, the most dangerous form of malaria, which—despite the successes by various international bodies and philanthropic organizations—still claims an annual death toll of 435,000 (World Health Organisation, 2018). These diseases disproportionally affect the poor and vulnerable populations (WHO Expert Committee on Malaria: Twentieth Report, n.d.), calling for action to improve global well-being. A key element of the fight against protozoan neglected tropical diseases and malaria is the discovery of novel chemotherapeutic agents
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