BackgroundMedicinal 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 Vernoniaamygdalina leaf extracts and isolated compounds against gametocytes and sporogonic stages of Plasmodiumberghei and to validate the findings on field isolates of Plasmodium falciparum.MethodsAqueous (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.ResultsVer-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.ConclusionsVernonia 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0812-2) contains supplementary material, which is available to authorized users.
Onchocerciasis is a disease of public health and socio-economic importance in Ethiopia. The aim of this study was to assess parasitological and clinico-epidemiological features of onchocerciasis in the Anfilo District, West Wellega, prior to implementation of Community Directed Treatment with Ivermectin (CDTI) to generate epidemiological and parasitological data for use in control program of the disease and subsequent evaluation of CDTI. A cross-sectional study was conducted in Anfilo District of West Wellega zone during a period of 1 month: from midAugust to mid-September 2006. Data on socio-demographic characteristics were collected using a standardized questionnaire prepared for this purpose. All persons were examined clinically for skin signs and symptoms of onchocerciasis. Two skin snips, one from each side of the gluteal fold were taken using blood lancet and sterilized razor blade and examined for microfilaria. All data were categorized, coded, entered in a data base and analyzed using SPSS version 15.0. for windows. A total of 1114 individuals C15 years were examined for microfilariae (mf) of Onchocerca volvulus and onchocercal skin disease (OSD). The prevalence of onchocercal (mf) carrier was 74.8% (833/1114). In both genders, the prevalence of onchocerciasis showed direct correlations with the age of individuals (R 2 = 0.79, P \ 0.05). The infection rate varied with the occupation of the study subjects, with preponderance among farmers. Among the subjects with onchocerciasis, the mf density ranged from 1.0 to 711.0 per mg of skin snip with a mean density (SD) and median values of 32.1 (61.5) and 10.4 respectively. The overall community microfilariae load (CMFL), the most sensitive parasitological indicator of onchocerciasis was 19.6. The pervasiveness of OSD among the study subjects was 26.4%. OSD was more frequent in males (32.4%) than their female counterparts (20.8%, P \ 0.05). The overall prevalence of onchocercal nodule carrier, the symptom opted for determining the community-wide prevalence of onchocerciasis was 12.1%. Leopard skin, the proxy of longstanding infection of onchocerciasis in the community, was also relatively high (19.1%). The abundance of mf in skin would definitely lead to high transmission potential in the Anfilo District. The situation in the Anfilo District should call for continued CDTI, owing to success of similar recommendations for such programmes in other parts of the country and elsewhere.
This study confirms, in the murine malaria system, the antiplasmodial properties of the examined remedies on the Plasmodium stages developing in the vertebrate host, thus encouraging studies aiming at identifying the active fractions and compounds responsible for the described activity and to develop standardized prophylactic remedies.
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