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Abstract Background This study was initiated to establish whether any South African ethnomedicinal plants (indigenous or exotic), that have been reported to be used traditionally to repel or kill mosquitoes, exhibit effective mosquito larvicidal properties. Methods Extracts of a selection of plant taxa sourced in South Africa were tested for larvicidal properties in an applicable assay. Thirty 3rd instar Anopheles arabiensis larvae were exposed to various extract types (dichloromethane, dichloromethane/methanol) (1:1), methanol and purified water) of each species investigated. Mortality was evaluated relative to the positive control Temephos (Mostop; Agrivo), an effective emulsifiable concentrate larvicide. Results Preliminary screening of crude extracts revealed substantial variation in toxicity with 24 of the 381 samples displaying 100% larval mortality within the seven day exposure period. Four of the high activity plants were selected and subjected to bioassay guided fractionation. The results of the testing of the fractions generated identified one fraction of the plant, Toddalia asiatica as being very potent against the An. arabiensis larvae. Conclusion The present study has successfully identified a plant with superior larvicidal activity at both the crude and semi pure fractions generated through bio-assay guided fractionation. These results have initiated further research into isolating the active compound and developing a malaria vector control tool.

Abstract Background Anti-malarial drug resistance threatens to undermine efforts to eliminate this deadly disease. The resulting omnipresent requirement for drugs with novel modes of action prompted a national consortium initiative to discover new anti-plasmodial agents from South African medicinal plants. One of the plants selected for investigation was Dicoma anomala subsp. gerrardii, based on its ethnomedicinal profile. Methods Standard phytochemical analysis techniques, including solvent-solvent extraction, thin-layer- and column chromatography, were used to isolate the main active constituent of Dicoma anomala subsp. gerrardii. The crystallized pure compound was identified using nuclear magnetic resonance spectroscopy, mass spectrometry and X-ray crystallography. The compound was tested in vitro on Plasmodium falciparum cultures using the parasite lactate dehydrogenase (pLDH) assay and was found to have anti-malarial activity. To determine the functional groups responsible for the activity, a small collection of synthetic analogues was generated - the aim being to vary features proposed as likely to be related to the anti-malarial activity and to quantify the effect of the modifications in vitro using the pLDH assay. The effects of the pure compound on the P. falciparum transcriptome were subsequently investigated by treating ring-stage parasites (alongside untreated controls), followed by oligonucleotide microarray- and data analysis. Results The main active constituent was identified as dehydrobrachylaenolide, a eudesmanolide-type sesquiterpene lactone. The compound demonstrated an in vitro IC50 of 1.865 μM against a chloroquine-sensitive strain (D10) of P. falciparum. Synthetic analogues of the compound confirmed an absolute requirement that the α-methylene lactone be present in the eudesmanolide before significant anti-malarial activity was observed. This feature is absent in the artemisinins and suggests a different mode of action. Microarray data analysis identified 572 unique genes that were differentially expressed as a result of the treatment and gene ontology analysis identified various biological processes and molecular functions that were significantly affected. Comparison of the dehydrobrachylaenolide treatment transcriptional dataset with a published artesunate (also a sesquiterpene lactone) dataset revealed little overlap. These results strengthen the notion that the isolated compound and the artemisinins have differentiated modes of action. Conclusions The novel mode of action of dehydrobrachylaenolide, detected during these studies, will play an ongoing role in advancing anti-plasmodial drug discovery efforts.

Abstract Background This study was conducted to evaluate whether a selection of South African ethnomedicinal plants included in this study displayed insecticidal properties when screened against adult stages of the mosquito. Methods 381 crude extracts of 80 plant taxa in 42 families were sprayed onto ceramic tiles and screened using the cone bio-assay method for insecticide efficacy testing. Blood-fed, female Anopheles arabiensis mosquitoes were exposed to the treated tiles for a period of sixty minutes. Mosquito mortality was monitored for twenty-four hours. Results Of all the extracts analysed, the highest activity was observed in Ptaeroxylon obliquum (Ptaeroxylaceae) and Pittosporum viridiflorum (Pittosporaceae), a single extract from each, exhibiting more than 50% mortality. A large proportion (81.63%) of the extracts tested displayed low levels of mosquitocidal activity. The remainder of the extracts (17.85%) exhibited no bioactivity (0% mortality). Conclusions The screening results have shown that in accordance with WHO standards, none of the crude extracts tested had exhibited greater than 60% mortality against the adult stages of the malaria vector Anopheles arabiensis.

Abstract Background This study was initiated to establish whether any South African ethnomedicinal plants (indigenous or exotic), that have been reported to be used traditionally to repel or kill mosquitoes, exhibit effective mosquito repellent properties. Methods Extracts of a selection of South African taxa were tested for repellency properties in an applicable mosquito feeding-probing assay using unfed female Anopheles arabiensis. Results Although a water extract of the roots of Chenopodium opulifolium was found to be 97% as effective as DEET after 2 mins, time lag studies revealed a substantial reduction in efficacy (to 30%) within two hours. Conclusions None of the plant extracts investigated exhibited residual repellencies >60% after three hours.