Evaluation of Cuspidaria pulchra and its Isolated Compounds Against Schistosoma mansoni Adult Worms

The present study has investigated the chemical composition of the bioactive EtOAc fraction of Cuspidaria pulchra aerial parts, as well as its schistosomicidal activities against Schistosoma mansoni adult worms in vitro. To this end, the crude ethanol extract obtained from the aerial parts of C. pulchra (Bignoniaceae) was partitioned with n-hexane, EtOAc, and n-BuOH. The EtOAc fraction was purified by preparative HPLC, which afforded 3,4-dihydroxybenzaldehyde (1), p-coumaric acid (2), p-hydroxybenzoic acid (3), ursolic acid (4), and oleanolic acid (5). The bioassay results indicated that the crude ethanol extract and the EtOAc fraction at 100 µg/mL killed the adult schistosomes in vitro. Compounds 1 and 3 at 100 µm were only able to separate coupled S. mansoni adult worms

In vitro schistosomicidal effects of the essential oil of Tagetes erecta

The in vitro schistosomicidal effects of the essential oil obtained from Tagetes erecta L. Asteraceae, leaves (TE-EO) collected in Brazil against Schistosoma mansoni worms are reported in this paper. The oil caused a significant decrease in the motor activity at 50 µg/mL as minimal concentration after 24 h. This oil also caused death of all the parasites and the separation of coupled pairs into individual male and female at 100 µg/mL after 24 h. The viability of adult worm groups treated with the TE-EO at 100 µg/mL was similar to that of groups treated with praziquantel (positive control). In addition, the oil promoted the inhibition of eggs development at all the tested concentrations. These data indicate that the TE-EO could be considered as a promising source for the development of new schistosomicidal agents

Chemical composition, antischistosomal and cytotoxic effects of the essential oil of Lavandula angustifolia grown in Southeastern Brazil

This paper reports on the chemical composition, the in vitro antischistosomal effects, and the cytotoxicity of the essential oil from the leaves of Lavandula angustifolia Mill., Lamiaceae, grown in the Southeastern Brazil. Borneol (22.4%), epi-α-muurolol (13.4%), α-bisabolol (13.1%), precocene I (13.0%), and eucalyptol (7.9%) were the major essential oil constituents. Incubation with essential oil at 200 μg/ml killed all the adult S. mansoni worms after 24 h (LC50 117.7 and 103.9 μg/ml at 24 and 120 h of incubation, respectively). At a concentration of 50 μg/ ml, the essential oil significantly decreased the motor activity and reduced the percentage of egg development after 120 h. In addition, the essential oil separated all the coupled S. mansoni worm pairs into individual male and female at 25 and 50 μg/ml within 120 and 24 h, respectively. This oil was cytotoxic to GM07492-A cells at only concentrations higher than 200 μg/ml (IC50 243.7 μg/ml). These data indicate that LA-EO exhibits moderate in vitro activity against adult S. mansoni and exerts remarkable effects on eggs development. Keywords: Schistosoma mansoni, Essential oil, Lavandula angustifolia, Lavandula officinali

In vitro anti-Trypanosoma cruzi activity enhancement of curcumin by its monoketone tetramethoxy analog diveratralacetone

Chagas disease is a tropical disease caused by the protozoan parasite Trypanosoma cruzi and currently affects millions of people worldwide. Curcumin (CUR), the major constituent of turmeric spice (dry powder of Curcuma longa L. plant rhizomes and roots), exhibits antiparasitic activity against protozoan parasites in vitro. However, because of its chemical instability, poor cellular uptake and limited bioavailability it is not suitable for clinical use. The objective of this study was to synthesize and evaluate in vitro CUR monoketone analog dibenzalacetone (DBA 1) and its non-phenolic, methoxy (2–4) and chloro (5) derivatives for better stability and bioavailability against T. cruzi. Diveratralacetone, the tetramethoxy DBA (DBA 3), was found to be the CUR analog with most enhanced activity against the amastigote forms of four strains of T. cruzi tested (Brazil, CA-I/72, Sylvio X10/4 and Sylvio X10/7) with 50% inhibitory concentration (IC50)  10 (C2C12 non-infected mammalian cells). This was supplemented by time-course assessment of its anti-T. cruzi activity. DBA 1 and its dimethoxy (DBA 2) and hexamethoxy (DBA 4) derivatives were substantially less active. The inactivity of dichloro-DBA (DBA 5) was indicative of the important role played by oxygenated groups such as methoxy in the terminal aromatic rings in the DBA molecule, particularly at para position to form reactive oxygen species essential for anti-T. cruzi activity. Although the DBAs and CUR were toxic to infected mammalian cells in vitro, in a mouse model, both DBA 3 and CUR did not exhibit acute toxicity or mortality. These results justify further optimization and in vivo anti-T. cruzi activity evaluation of the inexpensive diveratralacetone for its potential use in treating Chagas disease, a neglected parasitic disease in economically challenged tropical countries

Effect of MG-132 on gene expression profile in <i>Schistosoma mansoni</i> adult worms.

<p>Adult worm pairs were treated for 24 h with 50 μM MG-132. Microarrays were used to measure gene expression on a large scale. The figure shows a group of 1,919 genes with a statistically significant (<i>q-value</i> ≤ 0.025) differential expression in adult worms treated with MG-132 <i>versus</i> controls. Each horizontal line represents a gene and each column represents an experimental replicate. There are two technical replicates for each one of four biological replicates. Genes with transcription induced by treatment are shown in red, genes with repressed transcription are in green, and the color intensity is proportional to the log2 ratio (treated/control), as indicated by the color scale at the bottom.</p

Scanning electron microscopy of the tegument of <i>S</i>. <i>mansoni</i> adult worms.

<p>(A, x600) Normal morphology of adult worm tegument. (B, x1200) and (C, x3000) magnification of normal morphology of <i>S</i>. <i>mansoni</i> tegument showing the large number of tubercles (tu) and spines (sp). (D, x5000) Magnification of normal morphology of <i>S</i>. <i>mansoni</i> tegument showing spines (sp). (E, x600) Morphology of <i>S</i>. <i>mansoni</i> tegument after treatment with 50 μM MG-132 for 24 h. (F, x1200) Magnification showing tegumental changes in treated male adult worms: peeling (p), swelling (s), outbreak (o). (G, x3000) and (H, x5000) Magnification showing peeling (p) and bubbles (b) in the tegument promoted by MG-132.</p

Effects of (-)-6,6'-dinitrohinokinin on adult worms of Schistosoma mansoni: a proteomic analyses

Abstract Schistosomiasis, a chronic disease that affects million people worldwide, is caused by trematode flukes of the genus Schistosoma. The lack of an anti-schistosomiasis vaccine and massive monotherapy with praziquantel reinforces the need for search and development of new therapeutic drugs. Recently, we demonstrated that the essential oil of Piper cubeba L., Piperaceae, and their derivative dibenzylbutyrolactolic (-)-6,6'-dinitrohinokinin, presents in vitro and in vivo activities against Schistosoma mansoni. Here, we identified changes in the protein expression after exposure to dibenzylbutyrolactolic (-)-6,6'-dinitrohinokinin. We applied two-dimensional gel electrophoresis (2-DE) to S. mansoni soluble protein extracts and observed at least 38 spots to be affected by dibenzylbutyrolactolic (-)-6,6'-dinitrohinokinin. We further identified 25 differentially expressed proteins by mass spectrometry. Enrichment for biological processes and predictive analyses of protein-protein interactions suggest that dibenzylbutyrolactolic (-)-6,6'-dinitrohinokinin targets proteins involved mainly in metabolic processes, especially carbohydrate metabolism. In summary, this study provides an interesting approach to understand the anti-parasitic activity of semi-synthetic (-)-6,6'-dinitrohinokinin a derivative compound from lignan and for the development of new therapy strategies

Microarray results validation by real-time PCR.

<p>Validation is shown for a group of selected differentially expressed genes in <i>S</i>. <i>mansoni</i> adult worms treated with MG-132 compared with control parasites. Real time PCR data, expressed as Fold Change (normalized to the control group) are displayed as a bar graph while the corresponding data from the microarray (fold change) are shown below in numbers. The asterisk (*) indicates a statistically significant change (p < 0.05, t-test) when comparing treated with control samples.</p