In vitro anti-plasmodial activity of Dicoma anomala subsp. gerrardii (Asteraceae): identification of its main active constituent, structure-activity relationship studies and gene expression profiling

Abstract

BackgroundAnti-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.MethodsStandard 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.ResultsThe 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.ConclusionsThe novel mode of action of dehydrobrachylaenolide, detected during these studies, will play an ongoing role in advancing anti-plasmodial drug discovery efforts.

A Review of Medicinal Plants Used by the Basotho for Treatment of Skin Disorders: Their Phytochemical, Antimicrobial, and Anti-Inflammatory Potential

“…The majority of the plants used by the Basotho for the treatment of venereal sores are used for herpes (15), these include Agave americana, A. ferox, Buddleja salviifolia, Elephantorrhiza elephantina, L. sericea, M. parviflora, Olea europaea ssp. africana, and Searsia lancea, with only three used for syphilic sores, namely A. hispida, Monsonia brevirostrata, and Wahlenbergia banksiana, and one (Scabiosa columbaria), for the treatment of venereal (unspecified) sores.…”

“…Datura stramonium, Gunnera perpensa, R. prinoides, Salix mucronata, S. nigrum, and Withania somnifera for their chemical properties. Presence of a wide array of chemical compounds has been reported in several plants (number shown in brackets) including alkaloids (15), anthraquinones (8), coumarins (2), flavonoids (19), glycosides (17), saponins (15), tannins (14), and terpenoids (11). Many of these compounds are known to have several pharmacological effects such as anti-allergic, antibacterial, antifungal, anti-inflammatory, anti-mutagenic, antiplasmodial, antioxidant, and anti-tumour, to name but a few.…”

Modulation of Mutagen-Induced Genotoxicity by two Lesotho Medicinal Plants in Allium cepa L

“…Two subspecies of D. anomala occur in South Africa: D. anomala sub sp anomala and D. anomala subsp. gerrardii (Becker et al, 2011). Phytochemical investigations of D. anomala have identified several classes of secondary metabolites; including acetylenic compounds, phenolic acids, flavonoids, sesquiterpene lactones, triterpenes and phytosterols (Becker et al, 2011).…”

“…gerrardii (Becker et al, 2011). Phytochemical investigations of D. anomala have identified several classes of secondary metabolites; including acetylenic compounds, phenolic acids, flavonoids, sesquiterpene lactones, triterpenes and phytosterols (Becker et al, 2011). Dicoma anomala is used as a root decoction for blood disorders, colic, diarrhoea, dysentery, toothache, and purgative for intestinal worms (Kazembe & Chinyuku, 2012).…”

Bioactivity Screening of Erechtites valerianifolia (Link Ex Wolf.) Less. Extracts as Antiplasmodium, Antibacterial, Antifungal and Cytotoxic Agents

“…The study reported that the extract of plants in Asteraceae family has antimalarial activity against various types of Plasmodium. [3][4][5] In addition, a study in 2015 found that the extract of the family Asteraceae exhibits antioxidant and antibacterial activities. 6,7 The mechanism of action of antibacterial drugs is slightly similar to that of antifungal drugs and antimalarial/antiplasmodium; therefore, it is hypothesized that E. valerianifolia is likely to possess both antifungal and antiplasmodium activities.…”