Cardamonin Presents in Vivo Activity against Schistosoma mansoni and Inhibits Potato Apyrase.

Schistosomiasis, a neglected tropical disease caused by Schistosoma species, harms over 250 million people in several countries. The treatment is achieved with only one drug, praziquantel. Cardamonin, a natural chalcone with in vitro schistosomicidal activity, has not been in vivo evaluated against Schistosoma. In this work, we evaluated the in vivo schistosomicidal activities of cardamonin against Schistosoma mansoni worms and conducted enzymatic apyrase inhibition assay, as well as molecular docking analysis of cardamonin against potato apyrase, S. mansoni NTPDase 1 and S. mansoni NTPDase 2. In a mouse model of schistosomiasis, the oral treatment with cardamonin (400 mg/kg) showed efficacy against S. mansoni, decreasing the total worm load in 46.8 % and reducing in 54.5 % the number of eggs in mice. Cardamonin achieved a significant inhibition of the apyrase activity and the three-dimensional structure of the potato apyrase, obtained by homology modeling, showed that cardamonin may interact mainly through hydrogen bonds. Molecular docking studies corroborate with the action of cardamonin in binding and inhibiting both potato apyrase and S. mansoni NTPDases.

Assessment of the In Vitro Antischistosomal Activities of the Extracts and Compounds from Solidago Microglossa DC (Asteraceae) and Aristolochia Cymbifera Mart. & Zucc. (Aristolochiaceae).

Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is a neglected tropical disease that afflicts over 230 million people worldwide. Currently, treatment is achieved with only one drug, praziquantel (PZQ). In this regard, the roots of Solidago microglossa (Asteraceae) and Aristolochia cymbifera (Aristolochiaceae) are popularly used as anthelmintic. Despite their medicinal use against helminthiasis, such as schistosomiasis, A. cymbifera, and S. microglossa have not been evaluated against S. mansoni. Then, in this work, the in vitro antischistosomal activity of the crude extracts of A. cymbifera (Ac) and S. microglossa (Sm) and their isolated compounds were investigated against S. mansoni adult worms. Sm (200 µg/mL) and Ac (100-200 µg/mL) were lethal to all male and female worms at the 24 h incubation. In addition, Sm (10-50 µg/mL) and Ac (10 µg/mL) caused significant reduction in the parasite's movements, showing no significant cytotoxicity to Vero cells at the same range of schistosomicidal concentrations. Confocal laser scanning microscopy revealed that Sm and Ac caused tegumental damages and reduced the numbers of tubercles of male schistosomes. Chromatographic fractionation of Sm leads to isolation of bauerenol, α-amirin, and spinasterol, while populifolic acid, cubebin, 2-oxopopulifolic acid methyl ester, and 2-oxopopulifolic acid were isolated from Ac. At concentrations of 25-100 µM, bauerenol, α-amirin, spinasterol, populifolic acid, and cubebin showed significant impact on motor activity of S. mansoni. 2-oxopopulifolic acid methyl ester and 2-oxopopulifolic acid caused 100% mortality and decreased the motor activity of adult schistosomes at 100 µM. This study has reported, for the first time, the in vitro antischistosomal effects of S. microglossa and A. cymbifera extracts, also showing promising compounds against adult schistosomes.

In Vitro Schistosomicidal Activity of the Alkaloid-Rich Fraction from Ruta graveolens L. (Rutaceae) and Its Characterization by UPLC-QTOF-MS.

Schistosomiasis is a neglected tropical disease that affects million people worldwide, mostly in developing countries. Ruta graveolens (Rutaceae) is a plant used in folk medicine to treat several diseases, including parasitic infections. In this study, we reported the in vitro schistosomicidal activity of the R. graveolens extract (Rg) and its active fraction (Rg-FAE). Also, the characterization of Rg-FAE by UPLC-ESI-QTOF-MS analysis and its in vitro antileishmanial activity against Leishmania braziliensis were also performed. In vitro schistosomicidal assays were assessed against adult worms of S. mansoni, while cell viability against peritoneal macrophages was measured by MTT assay. Rg (100 µg/mL) exhibited noticeable schistosomicidal activity, causing 100% mortality and decreasing motor activity of all adult male and female schistosomes, but with low activity against L. braziliensis. After chromatographic fractionation of Rg, fraction Rg-FAE was obtained, showing high activity against adult schistosomes. UPLC-ESI-QTOF-MS analysis of Rg-FAE revealed the presence of eleven alkaloids and one furanocoumarin. No significant antileishmanial activity was found for Rg, while Rg-FAE exhibited activity against L. braziliensis promastigotes. We demonstrated, for the first time, that the R. graveolens extract (Rg) and its alkaloid-rich fraction (Rg-FAE) are active against adult worms of S. mansoni, with no significant cytotoxicity on macrophages. Our findings open the route to further antiparasitic studies with the active fraction of R. graveolens and its identified compounds, especially alkaloids.

Flavonoids and Sesquiterpene Lactones from Artemisia absinthium and Tanacetum parthenium against Schistosoma mansoni Worms.

Human schistosomiasis, caused by trematode worms of the genus Schistosoma, is one of the most significant neglected tropical diseases, affecting more than 200 million individuals worldwide and praziquantel is the only available drug to treat this disease. Artemisia absinthium L. and Tanacetum parthenium L. are species popularly used as anthelmintics. We investigated the in vitro schistosomicidal activity of crude extracts of A. absinthium (AA) and T. parthenium (TP) and their isolated compounds. AA and TP, at 200 µg/mL, were active, causing 100% mortality of all adult worms. Chromatographic fractionation of AA leads to isolation of artemetin and hydroxypelenolide, while santin, apigenin, and parthenolide were isolated from TP. Artemetin, hydroxypelenolide, santin, and apigenin, at 100 µM, were inactive against adult worms. Parthenolide (12.5 to 100 µM) caused 100% mortality, tegumental alterations, and reduction of motor activity of all adult worms of S. mansoni, without affecting mammalian cells. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms. This report provides the first evidence for the in vitro activity of parthenolide against adult worms of S. mansoni, opening the route to further schistosomicidal studies with this compound.