[PMID]: | 28945741 |
[Au] Autor: | Laurella LC; Cerny N; Bivona AE; Sánchez Alberti A; Giberti G; Malchiodi EL; Martino VS; Catalan CA; Alonso MR; Cazorla SI; Sülsen VP |
[Ad] Endereço: | Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Farmacognosia, Buenos Aires, Argentina. |
[Ti] Título: | Assessment of sesquiterpene lactones isolated from Mikania plants species for their potential efficacy against Trypanosoma cruzi and Leishmania sp. |
[So] Source: | PLoS Negl Trop Dis;11(9):e0005929, 2017 Sep. |
[Is] ISSN: | 1935-2735 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Four sesquiterpene lactones, mikanolide, deoxymikanolide, dihydromikanolide and scandenolide, were isolated by a bioassay-guided fractionation of Mikania variifolia and Mikania micrantha dichloromethane extracts. Mikanolide and deoxymikanolide were the major compounds in both extracts (2.2% and 0.4% for Mikania variifolia and 21.0% and 6.4% for Mikania micrantha respectively, calculated on extract dry weight). Mikanolide, deoxymikanolide and dihydromikanolide were active against Trypanosoma cruzi epimastigotes (50% inhibitory concentrations of 0.7, 0.08 and 2.5 µg/mL, for each compound respectively). These sesquiterpene lactones were also active against the bloodstream trypomastigotes (50% inhibitory concentrations for each compound were 2.1, 1.5 and 0.3 µg/mL, respectively) and against amastigotes (50% inhibitory concentrations for each compound were 4.5, 6.3 and 8.5 µg/mL, respectively). By contrast, scandenolide was not active on Trypanosoma cruzi. Besides, mikanolide and deoxymikanolide were also active on Leishmania braziliensis promastigotes (50% inhibitory concentrations of 5.1 and 11.5 µg/mL, respectively). The four sesquiterpene lactones were tested for their cytotoxicity on THP 1 cells. Deoxymikanolide presented the highest selectivity index for trypomastigotes (SI = 54) and amastigotes (SI = 12.5). In an in vivo model of Trypanosoma cruzi infection, deoxymikanolide was able to decrease the parasitemia and the weight loss associated to the acute phase of the parasite infection. More importantly, while 100% of control mice died by day 22 after receiving a lethal T. cruzi infection, 70% of deoxymikanolide-treated mice survived. We also observed that this compound increased TNF-α and IL-12 production by macrophages, which could contribute to control T. cruzi infection. |
[Mh] Termos MeSH primário: |
Lactonas/farmacologia Leishmania braziliensis/efeitos dos fármacos Mikania/química Extratos Vegetais/farmacologia Sesquiterpenos/farmacologia Trypanosoma cruzi/efeitos dos fármacos
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[Mh] Termos MeSH secundário: |
Animais Doença de Chagas/tratamento farmacológico Doença de Chagas/parasitologia Descoberta de Drogas Interleucina-12/biossíntese Interleucina-12/imunologia Lactonas/administração & dosagem Lactonas/química Lactonas/isolamento & purificação Lactonas/uso terapêutico Estágios do Ciclo de Vida/efeitos dos fármacos Masculino Camundongos Camundongos Endogâmicos BALB C Extratos Vegetais/química Sesquiterpenos/química Sesquiterpenos/isolamento & purificação Sesquiterpenos de Germacrano/administração & dosagem Sesquiterpenos de Germacrano/isolamento & purificação Sesquiterpenos de Germacrano/farmacologia Sesquiterpenos de Germacrano/uso terapêutico Trypanosoma cruzi/isolamento & purificação Fator de Necrose Tumoral alfa/biossíntese Fator de Necrose Tumoral alfa/imunologia
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (1,10:2,3-diepoxy-6,8-dihydroxy-11-vinylgermacr-4-ene 12,14-di-gamma-lactone); 0 (Lactones); 0 (Plant Extracts); 0 (Sesquiterpenes); 0 (Sesquiterpenes, Germacrane); 0 (Tumor Necrosis Factor-alpha); 0 (deoxymikanolide); 187348-17-0 (Interleukin-12); 23758-16-9 (scandenolide) |
[Em] Mês de entrada: | 1710 |
[Cu] Atualização por classe: | 171025 |
[Lr] Data última revisão:
| 171025 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170926 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1371/journal.pntd.0005929 |
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