Pharmaceutics
·
2022
·Vol. 14
·期 5
·1071
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IF 6.525
Lara Soares Aleixo de Carvalho,Vinícius Carius de Souza,Vinícius C. Rodrigues,Aline Correa Ribeiro,Jorge Willian Leandro Nascimento,Priscila V. S. Z. Capriles,Priscila de F. Pinto,Josué de Moraes,Ademar Alves da Silva Filho
Schistosomiasis, caused by parasites of the genusSchistosoma, is a neglected disease with high global prevalence, affecting more than 240 million people in several countries. Praziquantel (PZQ) is the only drug currently available for the treatment.S. mansoniNTPDases (known as SmNTPDases, ATP diphosphohydrolases orecto-apyrases) are potential drug targets for the discovery of new antischistosomal drugs. In this study, we screen NTPDases inhibitors fromCentella erecta(Apiaceae) using an ultrafiltration combined UHPLC-QTOF-MS method and potato apyrase, identifying asiaticoside as one of the apyrase-binding compounds. After isolation of asiaticoside fromC. erectaextract, we assessed its in vivo antischistosomal activities againstSchistosoma mansoniworms and its in vitro enzymatic apyrase inhibition. Also, molecular docking analysis of asiaticoside against potato apyrase,S. mansoniNTPDases 1 and 2 were performed. Asiaticoside showed a significant in vitro apyrase inhibition and molecular docking studies corroborate with its possible actions in potato apyrase andS. mansoniNTPDases. In mice harboring a patentS. mansoniinfection, a single oral dose of asiaticoside (400 mg/kg. p.o.) showed significantly in vivo antischistosomal efficacy, markedly decreasing the total worm load and egg burden, giving support for further exploration of apyrase inhibitors as antischistosomal agents.Keywords:Schistosoma mansoni;natural products;asiaticoside
研究领域:
药理学
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寄生虫学
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天然产物研究
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DOI
PubMed
高影响因子
Pharmaceutics
·
2026
·Vol. 18
·期 6
·694
·
IF 6.9
José Márcio Fernandes da Silva,Dominique Mesquita e Silva,Danilo de Souza Costa,Monique C. Amaro,Rayssa A. Cajas,Josué de Moraes,Guilherme Diniz Tavares,Ademar Alves Da Silva Filho
Background:Schistosomiasis remains a major neglected tropical disease, with praziquantel (PZQ) as the only widely used treatment, despite its limitations. Parthenolide (PTL), a sesquiterpene lactone, exhibits potent in vitro antischistosomal activity; however, its poor aqueous solubility, low oral bioavailability, and chemical instability may limit its in vivo efficacy.Objective:This study investigated whether nanoencapsulation in nanostructured lipid carriers (NLC) could enable the in vivo antischistosomal activity of PTL.Methods:PTL was isolated fromTanacetum partheniumand incorporated into NLC using hot emulsification followed by ultrasonication. The resulting formulation (NLC-PTL) was physicochemically characterized, and its in vivo antischistosomal efficacy was evaluated in a murine model ofSchistosoma mansoniinfection.Results:NLC-PTL exhibited nanoscale size, low polydispersity, high encapsulation efficiency, and sustained drug release. In vivo, free PTL showed no significant effect on worm burden, whereas NLC-PTL achieved a marked reduction (77.9%) in adult worms and significantly decreased egg output compared to controls (p< 0.001). Blank NLC had no antiparasitic effect.Conclusions:Nanoencapsulation was associated with in vivo antischistosomal activity of PTL compared to the free compound. These findings suggest that formulation strategies may influence the in vivo performance of lipophilic natural products in schistosomiasis.
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Danilo de Souza Costa,Rayssa A. Cajas,Carla Monteiro Leal,Lara S. Aleixo de Carvalho,Lara Cruz de Souza,Lucas Fukui-Silva,Josué de Moraes,Ademar A. Da Silva Filho
Ethnopharmacological relevance Acmella oleracea (L.) R. K. Jansen, commonly referred to as “Jambu”, is a valuable medicinal plant native to the Amazon regions. Inflorescences of A. oleracea is utilized as local anesthetic properties and for its insecticidal, antiparasitic, and anthelmintic attributes. Aims of this study This study aimed to evaluate the in vitro and in vivo antiparasitic properties of A. oleracea extract and spilanthol (SPL) against Schistosoma mansoni . Materials and methods The ethanolic extract of A. oleracea inflorescences (AoE) was prepared, analyzed by HPLC-DAD, and characterized by UHPLC-HRMS/MS. SPL was isolated from AoE by chromatographic fractionation. The antischistosomal properties of AoE and SPL were evaluated in vitro against adult schistosomes and in preclinical assays using murine models of patent S. mansoni infection. Results Through UHPLC-HRMS/MS analysis, 14 alkamides were annotated in AoE. HPLC-DAD analysis of AoE revealed a peak with a substantial relative area of ∼85%, which was isolated and identified as SPL. AoE and SPL caused mortality of adult schistosomes ex vivo , showing EC 50 values of 32.6 μg/mL and 27.8 μM, respectively, without affected Vero cells or Caenorhabditis elegans . In preclinical studies, the oral administration (400 mg/kg) of AoE and SPL resulted in significant reductions in worm burden of 28% and ∼42%, respectively. Additionally, SPL exhibits remarkable effects on oogram, decreasing egg burden and the number of immature eggs by over 80%, while also promoting significant reductions in hepato- and splenomegaly. Conclusions The research underscores the antischistosomal activity of A. oleracea highlighting the potential of SPL as a lead for the development of new schistosomicidal drugs and encouraging further studies to validate the traditional anthelmintic use of A. oleracea inflorescences.
研究领域:
药理学
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寄生虫学
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药物开发
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Danilo de Souza Costa,Carla Monteiro Leal,Rayssa A. Cajas,Matheus Coutinho Gazolla,Lívia Mara Silva,Lara Soares Aleixo de Carvalho,Bruna L. Lemes,Renato Oliveira de Moura,Juliana de Almeida,Josué de Moraes,Ademar A. da Silva Filho
Ethnopharmacological relevance Roots of Pothomorphe umbellata (L.) Miq. are used in traditional medicine of Africa and South America for the treatment of malaria and helminthiasis . However, neither P. umbellata nor its isolated compounds have been evaluated against Schistosoma species. Aims of this study To investigate the antischistosomal effects of P. umbellata root extracts and the isolated compound 4-nerolidylcatechol (4-NC) against Schistosoma mansoni ex vivo and in murine models of schistosomiasis. Materials and methods The crude hydroalcoholic (PuE) and hexane (PuH) extracts of P. umbellata roots were prepared and initially submitted to an ex vivo phenotypic screening against adult S. mansoni . PuH was analyzed by HPLC-DAD, characterized by UHPLC-HRMS/MS, and submitted to chromatographic fractionation, leading to the isolation of 4-NC. The anthelmintic properties of 4-NC were assayed ex vivo against adult schistosomes and in murine models of schistosomiasis for both patent and prepatent S. mansoni infections. Praziquantel (PZQ) was used as a reference compound. Results PuE (EC 50 : 18.7 μg/mL) and PuH (EC 50 : 9.2 μg/mL) kill adult schistosomes ex vivo . The UHPLC–HRMS/MS analysis of PuH, the most active extract, revealed the presence of 4-NC, peltatol A, and peltatol B or C. After isolation from PuH, 4-NC presented remarkable in vitro schistosomicidal activity with EC 50 of 2.9 μM (0.91 μg/mL) and a selectivity index higher than 68 against Vero mammalian cells, without affecting viability of nematode Caenorhabditis elegans . In patent S. mansoni infection, the oral treatment with 4-NC decreased worm burden and egg production in 52.1% and 52.3%, respectively, also reducing splenomegaly and hepatomegaly . 4-NC, unlike PZQ, showed in vivo efficacy against juvenile S. mansoni , decreasing worm burden in 52.4%. Conclusions This study demonstrates that P. umbellata roots possess antischistosomal activity, giving support for the medicinal use of this plant against parasites. 4-NC was identified from P. umbellata roots as one of the effective in vitro and in vivo antischistosomal compound and as a potential lead for the development of novel anthelmintics.
研究领域:
民族药理学
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寄生虫学
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药物化学
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产品关联
DOI
PubMed
高影响因子
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