BACKGROUND : 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. 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.
METHODS : A 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.
RESULTS : Two 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.
CONCLUSION : This 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
Additional file 1: Table S1. Inhibition of in vitro viability of late stage
gametocytes of Plasmodium falciparum (NF54 strain) by crude extract and
fractions of Artemisia afra. Table S2. Inhibition of Plasmodium falciparum
late gametocyte stages by fractions from column 1. Table S3. IC50
of Artemisia afra chloroform fraction, compounds 1 and 2 on intra-erythrocytic
asexuals, early gametocytes and late stage gametocytes. Fig. S1.
Base Peak Ion chromatograms from UPLC-MS analysis using ESI +ve mode
for fractions A) F10, B) F11, C) F13 and D) F19. Fig. S2. Full dose-response
curve plots for artemisinin (ART) and methylene blue (MB) against latestage
Plasmodium falciparum gametocytes.