In vivo antischistosomal efficacy of Porcelia ponderosa γ-lactones

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Souza, Dalete Christine S. ; Totini, Carlos H. ; Cajas, Rayssa A. ; Teixeira, Thaina R. ; Oliveira, Emerson A. ; Cirino, Maria E. ; Souza, Maria C. ; Salvadori, Maria C. ; Teixeira, Fernanda S. ; de Moraes, Josue ; Lago, Joao Henrique G.

• Tipo de documento: Artigo Científico
• Fonte: Phytomedicine; v. 135, p. 9-pg., 2024-09-18.

Resumo

Background: Schistosomiasis, caused by the parasitic blood fluke Schistosoma mansoni, , is a significant global health concern, particularly in tropical and subtropical regions. The available chemotherapeutic drug is restricted to praziquantel with present problems related to efficacy, toxicity and resistance, justifying the search for new drugs. Different natural products, including gamma-lactones, have demonstrated anthelmintic activity. Thus, in this study, new gamma-lactones from Porcelia ponderosa were investigated for their anti-S. S. mansoni effects in vitro and in vivo. . Purpose: To evaluate the therapeutical potential against S. mansoni of the mixture of gamma-lactones 1 + 2 obtained from Porcelia ponderosa seeds. Study design and methods: The precipitate formed during the concentration of CH2Cl2 2 Cl 2 extract from seeds of P. ponderosa showed to be composed by a mixture of the new gamma-lactones 1 + 2 (in a ratio 77:23) which were chemically characterized using NMR and ESI-HRMS. This mixture was evaluated in vitro and in vivo against S. mansoni, , using a murine model of schistosomiasis. Additionally, toxicity of the mixture of 1 + 2 (77:23) was determined using mammalian cell lines (in in vitro) ) or the model organism Caenorhabditis elegans (in in vivo). ). Results: Seeds of P. ponderosa afforded a mixture of two unreported gamma-lactones, 3-hydroxy-4-methylene-2-(tetracosa-17 ' Z,23 '-diene-13 ',15 '-diynyl)-but-2-enolide ' Z ,23 '-diene-13 ' ,15 '-diynyl)-but-2-enolide (1) 1 ) and 3-hydroxy-4-methylene-2-(tetracos-17 ' Z-ene-13 ',15 '- ' Z-ene-13 ' ,15 '- diynyl)-but-2-enolide (2). 2 ). Initially, the antischistosomal activity of the mixture of 1 + 2 (77:23) was investigated in vitro, and obtained results demonstrate reduced activity against Schistosoma mansoni worms (EC50 50 of 83.3 mu g/ ml) in comparison to positive control praziquantel (EC50 50 of 1.5 mu g/ml). However, when tested in vivo using oral administration at 400 mg kg-1 , the standard dose used in the murine model of schistosomiasis, the mixture of 1 + 2 (77:23) revealed expressive reductions in both worm burden (65.7 %) and egg production (97.2 %), similar of those observed to praziquantel (89.7 % and 91.5 %, respectively). On the other hand, when treated using 200 and 100 mg kg-1 , reductions in worm burden (25.7 and 12.4 %) and egg production (33.6 and 13.3 %) were also observed. Importantly, the mixture of 1 + 2 (77:23) exhibited no toxicity using mammalian cell lines (in in vitro) ) or C. elegans ( in vivo). ). Conclusion: Considering the promising in vivo activity of gamma-lactones from P. ponderosa, the mixture of 1 + 2 (77:23) can be considered as promising candidate for the development of novel antischistosomal therapeutics, (AU)

• Processo FAPESP: 23/08418-6 - Busca de metabólitos bioativos oriundos da biodiversidade brasileira como candidatos a fármacos para doenças causadas por helmintos
• Beneficiário: Josué de Moraes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 23/12447-1 - Busca de metabólitos especializados oriundos da biodiversidade florística brasileira como candidatos a fármacos para doenças tropicais negligenciadas
• Beneficiário: João Henrique Ghilardi Lago
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular