Abstract
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.
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The datasets generated during the current study are available from the corresponding author on reasonable request.
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Funding
The authors thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES—finance code no 001) and the Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco (FACEPE). H.A.D. Araújo and I.J. Cruz Filho would like to thank the FACEPE for the Regional Science Development Scholarship (Process DCR-0015–4.03/23) and the Researcher Fixation Scholarships (Process BFP-0038–4.03/21), respectively. In addition, H.D.A. Araújo and A.L. Aires would like to thank the FACEPE Research Project Aid (APQ-0037–4.03/23 and Process APQ-Emergent 1181–4.03/22, respectively).
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M.S.S. Silva, H.D.A. Araújo, and A.L. Aires made substantial contributions to the design of the work and study protocol. M.S.S. Silva, M.L.M.F. Santos, A.M. Silva, W.W.M. França, S.B. Araújo, R.L. Silva, W.R.C. Nascimento, N.P.S. Santos, I.J. Cruz Filho, M.C.P.A. Albuquerque, H.D.A. Araújo, and A.L. Aires carried out the assays and/or were involved in the analysis and interpretation of all data. M.S.S. Silva, I.J. Cruz Filho, H.D.A. Araújo, and A.L. Aires contributed to drafting the manuscript and/or critically revising the paper and intellectual content. All authors read and approved the final manuscript.
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de Souza Silva, M.S., dos Santos, M.L.M.F., da Silva, A.M. et al. 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). Parasitol Res 123, 143 (2024). https://doi.org/10.1007/s00436-024-08153-w
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DOI: https://doi.org/10.1007/s00436-024-08153-w