Abstract
BackgroundOptimal adoption of the malaria transmission-blocking strategy is currently limited by lack of safe and efficacious drugs. This has sparked the exploration of different sources of drugs in search of transmission-blocking agents. While plant species have been extensively investigated in search of malaria chemotherapeutic agents, comparatively less effort has been channelled towards exploring them in search of transmission-blocking drugs. Artemisia afra (Asteraceae), a prominent feature of South African folk medicine, is used for the treatment of a number of diseases, including malaria. In search of transmission-blocking compounds aimed against Plasmodium parasites, the current study endeavoured to isolate and identify gametocytocidal compounds from A. afra.MethodsA bioassay-guided isolation approach was adopted wherein a combination of solvent–solvent partitioning and gravity column chromatography was used. Collected fractions were continuously screened in vitro for their ability to inhibit the viability of primarily late-stage gametocytes of Plasmodium falciparum (NF54 strain), using a parasite lactate dehydrogenase assay. Chemical structures of isolated compounds were elucidated using UPLC-MS/MS and NMR data analysis.ResultsTwo guaianolide sesquiterpene lactones, 1α,4α-dihydroxybishopsolicepolide and yomogiartemin, were isolated and shown to be active (IC50 < 10 μg/ml; ~ 10 μM) against both gametocytes and intra-erythrocytic asexual P. falciparum parasites. Interestingly, 1α,4α-dihydroxybishopsolicepolide was significantly more potent against late-stage gametocytes than to early-stage gametocytes and intra-erythrocytic asexual P. falciparum parasites. Additionally, both isolated compounds were not overly cytotoxic against HepG2 cells in vitro.ConclusionThis study provides the first instance of isolated compounds from A. afra against P. falciparum gametocytes as a starting point for further investigations on more plant species in search of transmission-blocking compounds.
Highlights
Optimal adoption of the malaria transmission-blocking strategy is currently limited by lack of safe and efficacious drugs
Artemisinin derivatives play a pivotal role in malaria control where they are used as main partner drugs in artemisinin-based combination therapy (ACT), which currently serve as first-line treatment drugs for malaria [5]
The chloroform fraction was potently active against late-stage gametocytes, inhibiting viability of these P. falciparum parasites at 56–99%, compared to 9–21% inhibition seen with the crude extract (Fig. 1a)
Summary
Optimal adoption of the malaria transmission-blocking strategy is currently limited by lack of safe and efficacious drugs. This has sparked the exploration of different sources of drugs in search of transmission-blocking agents. The use of primaquine, the only World Health Organization-recommended malaria transmission-blocking drug, is severely restricted by its toxicity [10] This limited armoury of transmission-blocking drugs has necessitated exploration of different sources of drugs in search of novel compounds that are potent against gametocyte stages of Plasmodium parasites [11,12,13,14,15,16]. One potential vast source that still remains relatively unscrutinized in this effort is medicinal plant species [17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
