Sanguinarine: an alkaloid with promising in vitro and in vivo antiparasitic activity against different developmental stages of Schistosoma mansoni and in silico pharmacokinetic properties (ADMET).

The objective of the study was to evaluate the in vitro and in vivo schistosomicidal activity of sanguinarine (SA) on Schistosoma mansoni and its in silico pharmacokinetic parameters. ADMET parameters and oral bioavailability were evaluated using the PkCSM and SwissADME platforms, respectively. The activity of SA in vitro, at the concentrations of 1.0-25 µM, was analyzed through the parameters of motility, mortality, and cell viability of the worms at intervals of 3-24 h. Mice were infected with cercariae and treated by gavage with SA (5 mg/kg/day, in a single dose or two doses of 2.5 mg/kg every 12 h for 5 consecutive days) on the 1st (skin schistosomula), 14th (pulmonary schistosomula), 28th (young worms), and 45th (adult worms) days after infection. In vitro and in vivo praziquantel was the control. In vitro, SA showed schistosomicidal activity against schistosomula, young worms, and couples; with total mortality and reduced cell viability at low concentrations and incubation time. In a single dose of 5 mg/kg/day, SA reduces the total worm load by 47.6%, 54%, 55.2%, and 27.1%, and female worms at 52.0%, 39.1%, 52.7%, and 20.2%, respectively, results which are similar to the 2.5 mg/kg/day dose. SA reduced the load of eggs in the liver, and in histopathological and histomorphometric analyses, there was a reduction in the number and volume of hepatic granulomas, which exhibited less inflammatory infiltrate. SA has promising in vitro and in vivo schistosomicidal activity against different developmental stages of S. mansoni, in addition to reducing granulomatous liver lesions. Furthermore, in silico, SA showed good predictive pharmacokinetic ADMET profiles.

Toxic, cytotoxic and genotoxic effect of plumbagin in the developmental stages of Biomphalaria glabrata (Say, 1818-intermediate host) and cercaricidal activity against the infectious agent of schistosomiasis mansoni.

BACKGROUND: Snails of the genus Biomphalaria are intermediate hosts of Schistosoma mansoni, the main etiological agent of schistosomiasis mansoni, which affects about 236.6 million people in tropical and subtropical regions of the world. The World Health Organization recommends the population control of vector snails as one of the strategies to reduce the prevalence and incidence of schistosomiasis. In this study, molluscicidal and antiparasitic activities of plumbagin, a naturally sourced naphthoquinone with a range of biological effects, were evaluated against B. glabrata and cercariae of S. mansoni. RESULTS: After 24 h of exposure, plumbagin demonstrated molluscicidal activity at low concentrations against embryos (LC50 of 0.56, 0.93, 0.68, 0.51 and 0.74 µg mL-1 for the blastula, gastrula, trochophore, veliger and hippo stage, respectively) and adult snails (LC50 of 3.56 µg mL-1 ). There were no changes in exposed snails' fecundity or fertility; however, plumbagin was able to increase the frequency of DNA damage and the number of hemocytes, with apoptosis and binucleation being the main hemocyte alterations. In addition, plumbagin showed death of S. mansoni cercariae in the concentration of 1.5 µg mL-1 in 60 min, while showing moderate toxicity to Artemia salina. CONCLUSION: Plumbagin proved to be a promising substance for the control of B. glabrata population, intermediate host of S. mansoni, as well as the cercariae, infective stage for humans (definitive host), while being moderately toxic to A. salina, a crustacean widely used in ecotoxicity tests. © 2022 Society of Chemical Industry.

In vitro and in vivo evaluation of Bacillus clausii against Schistosoma mansoni.

Experimental studies and clinical trials have been showing that probiotics are promising in the prevention and control of parasite infections. B. clausii, obtained from Enterogermina®, was cultured to obtain cell-free culture supernatant (CFS) and spores to evaluate its schistosomicidal effect in vitro and in vivo against Schistosoma mansoni, respectively. For in vitro and in vivo analysis mice were infected with 120 and 50 cercariae, respectively. Couples of adult worms, recovered on day 45 of infection, were exposed to CFS. The in vivo assay was performed for 100 days, where all animals were infected on the 30th day. Four experimental groups were formed, as follows: G1 - Saline solution from the 1st until the 100th day; G2 - B. clausii from the 1st until the 100th day; G3 - B. clausii from the 68th day (onset of oviposition) until the 100th day and G4 - PZQ (50 mg/Kg) from the 75th until the 79th day. In vitro, CFS of B. clausii does not caused mortality nor changed the motility on S. mansoni adult worms. G2 and G3 showed reduction of the 68.58 and 44.25% in the number of eggs eliminated in the feces and 34.29 and 53.6% and 22.8 and 48.49% the number of eggs trapped in the liver and intestine, respectively. Furthermore, in both therapeutic regimens G2 and G3, B. clausii increased the percentage of dead eggs in the intestinal tissue. B. clausii CFS, in vitro, does not showed action against S. mansoni and that treatment with B. clausii spores modulates favorably the parasitological parameters in the experimental infection of S. mansoni.