Title |
Plasmodium transmission blocking activities of Vernonia amygdalina extracts and isolated compounds
|
---|---|
Published in |
Malaria Journal, July 2015
|
DOI | 10.1186/s12936-015-0812-2 |
Pubmed ID | |
Authors |
Solomon M Abay, Leonardo Lucantoni, Nisha Dahiya, Geme Dori, Edson G Dembo, Fulvio Esposito, Guilio Lupidi, Sonny Ogboi, Robert K Ouédraogo, Annamaria Sinisi, Orazio Taglialatela-Scafati, R Serge Yerbanga, Massimo Bramucci, Luana Quassinti, Jean Bosco Ouédraogo, George Christophides, Annette Habluetzel |
Abstract |
Medicinal plants are a validated source for discovery of new leads and standardized herbal medicines. The aim of this study was to assess the activity of Vernonia amygdalina leaf extracts and isolated compounds against gametocytes and sporogonic stages of Plasmodium berghei and to validate the findings on field isolates of Plasmodium falciparum. Aqueous (Ver-H2O) and ethanolic (Ver-EtOH) leaf extracts were tested in vivo for activity against sexual and asexual blood stage P. berghei parasites. In vivo transmission blocking effects of Ver-EtOH and Ver-H2O were estimated by assessing P. berghei oocyst prevalence and density in Anopheles stephensi mosquitoes. Activity targeting early sporogonic stages (ESS), namely gametes, zygotes and ookinetes was assessed in vitro using P. berghei CTRPp.GFP strain. Bioassay guided fractionation was performed to characterize V. amygdalina fractions and molecules for anti-ESS activity. Fractions active against ESS of the murine parasite were tested for ex vivo transmission blocking activity on P. falciparum field isolates. Cytotoxic effects of extracts and isolated compounds vernolide and vernodalol were evaluated on the human cell lines HCT116 and EA.hy926. Ver-H2O reduced the P. berghei macrogametocyte density in mice by about 50% and Ver-EtOH reduced P. berghei oocyst prevalence and density by 27 and 90%, respectively, in An. stephensi mosquitoes. Ver-EtOH inhibited almost completely (>90%) ESS development in vitro at 50 μg/mL. At this concentration, four fractions obtained from the ethylacetate phase of the methanol extract displayed inhibitory activity >90% against ESS. Three tested fractions were also found active against field isolates of the human parasite P. falciparum, reducing oocyst prevalence in Anopheles coluzzii mosquitoes to one-half and oocyst density to one-fourth of controls. The molecules and fractions displayed considerable cytotoxicity on the two tested cell-lines. Vernonia amygdalina leaves contain molecules affecting multiple stages of Plasmodium, evidencing its potential for drug discovery. Chemical modification of the identified hit molecules, in particular vernodalol, could generate a library of druggable sesquiterpene lactones. The development of a multistage phytomedicine designed as preventive treatment to complement existing malaria control tools appears a challenging but feasible goal. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 50% |
Science communicators (journalists, bloggers, editors) | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
Uganda | 1 | <1% |
Unknown | 116 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 18 | 15% |
Lecturer | 13 | 11% |
Student > Bachelor | 12 | 10% |
Researcher | 11 | 9% |
Student > Master | 11 | 9% |
Other | 24 | 20% |
Unknown | 29 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Pharmacology, Toxicology and Pharmaceutical Science | 22 | 19% |
Agricultural and Biological Sciences | 21 | 18% |
Medicine and Dentistry | 13 | 11% |
Biochemistry, Genetics and Molecular Biology | 9 | 8% |
Chemistry | 6 | 5% |
Other | 14 | 12% |
Unknown | 33 | 28% |