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Assessment of sesquiterpene lactones isolated from Mikania plants species for their potential efficacy against Trypanosoma cruzi and Leishmania sp.
PLoS Negl Trop Dis. 2017 Sep; 11(9):e0005929.PN

Abstract

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.

Authors+Show Affiliations

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Farmacognosia, Buenos Aires, Argentina.CONICET-Universidad Nacional de Luján, Instituto de Ecología y Desarrollo Sustentable (INEDES), Luján, Argentina.Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Inmunología, Buenos Aires, Argentina, Instituto de Estudios de la Inmunidad Humoral (IDEHU), UBA-CONICET, Buenos Aires, Argentina. CONICET- Universidad de Buenos Aires, Instituto de Microbiología y Parasitología Médica-CONICET (IMPaM), Facultad de Medicina, Piso 13, Buenos Aires, Argentina.Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Inmunología, Buenos Aires, Argentina, Instituto de Estudios de la Inmunidad Humoral (IDEHU), UBA-CONICET, Buenos Aires, Argentina. CONICET- Universidad de Buenos Aires, Instituto de Microbiología y Parasitología Médica-CONICET (IMPaM), Facultad de Medicina, Piso 13, Buenos Aires, Argentina.Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Farmacognosia, Buenos Aires, Argentina. CONICET-Universidad de Buenos Aires, Instituto de Química y Metabolismo del Fármaco-CONICET (IQUIMEFA), Buenos Aires, Argentina.Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Inmunología, Buenos Aires, Argentina, Instituto de Estudios de la Inmunidad Humoral (IDEHU), UBA-CONICET, Buenos Aires, Argentina. CONICET- Universidad de Buenos Aires, Instituto de Microbiología y Parasitología Médica-CONICET (IMPaM), Facultad de Medicina, Piso 13, Buenos Aires, Argentina.CONICET-Universidad de Buenos Aires, Instituto de Química y Metabolismo del Fármaco-CONICET (IQUIMEFA), Buenos Aires, Argentina.CONICET-Universidad Nacional de Tucumán, Instituto de Química del Noroeste-CONICET (INQUINOA), Ayacucho 471 (T4000INI), San Miguel de Tucumán, Argentina.CONICET-Universidad de Buenos Aires, Instituto de Química y Metabolismo del Fármaco-CONICET (IQUIMEFA), Buenos Aires, Argentina.CONICET- Universidad de Buenos Aires, Instituto de Microbiología y Parasitología Médica-CONICET (IMPaM), Facultad de Medicina, Piso 13, Buenos Aires, Argentina. CONICET-Centro de Referencia para Lactobacilos (CERELA), Batalla de Chacabuco 145, San Miguel de Tucumán, Argentina.Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Farmacognosia, Buenos Aires, Argentina. CONICET-Universidad de Buenos Aires, Instituto de Química y Metabolismo del Fármaco-CONICET (IQUIMEFA), Buenos Aires, Argentina.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28945741

Citation

Laurella, Laura C., et al. "Assessment of Sesquiterpene Lactones Isolated From Mikania Plants Species for Their Potential Efficacy Against Trypanosoma Cruzi and Leishmania Sp." PLoS Neglected Tropical Diseases, vol. 11, no. 9, 2017, pp. e0005929.
Laurella LC, Cerny N, Bivona AE, et al. Assessment of sesquiterpene lactones isolated from Mikania plants species for their potential efficacy against Trypanosoma cruzi and Leishmania sp. PLoS Negl Trop Dis. 2017;11(9):e0005929.
Laurella, L. C., Cerny, N., Bivona, A. E., Sánchez Alberti, A., Giberti, G., Malchiodi, E. L., Martino, V. S., Catalan, C. A., Alonso, M. R., Cazorla, S. I., & Sülsen, V. P. (2017). Assessment of sesquiterpene lactones isolated from Mikania plants species for their potential efficacy against Trypanosoma cruzi and Leishmania sp. PLoS Neglected Tropical Diseases, 11(9), e0005929. https://doi.org/10.1371/journal.pntd.0005929
Laurella LC, et al. Assessment of Sesquiterpene Lactones Isolated From Mikania Plants Species for Their Potential Efficacy Against Trypanosoma Cruzi and Leishmania Sp. PLoS Negl Trop Dis. 2017;11(9):e0005929. PubMed PMID: 28945741.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessment of sesquiterpene lactones isolated from Mikania plants species for their potential efficacy against Trypanosoma cruzi and Leishmania sp. AU - Laurella,Laura C, AU - Cerny,Natacha, AU - Bivona,Augusto E, AU - Sánchez Alberti,Andrés, AU - Giberti,Gustavo, AU - Malchiodi,Emilio L, AU - Martino,Virginia S, AU - Catalan,Cesar A, AU - Alonso,María Rosario, AU - Cazorla,Silvia I, AU - Sülsen,Valeria P, Y1 - 2017/09/25/ PY - 2017/06/23/received PY - 2017/09/04/accepted PY - 2017/10/05/revised PY - 2017/9/26/pubmed PY - 2017/10/27/medline PY - 2017/9/26/entrez SP - e0005929 EP - e0005929 JF - PLoS neglected tropical diseases JO - PLoS Negl Trop Dis VL - 11 IS - 9 N2 - 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. SN - 1935-2735 UR - https://www.unboundmedicine.com/medline/citation/28945741/Assessment_of_sesquiterpene_lactones_isolated_from_Mikania_plants_species_for_their_potential_efficacy_against_Trypanosoma_cruzi_and_Leishmania_sp_ L2 - http://dx.plos.org/10.1371/journal.pntd.0005929 DB - PRIME DP - Unbound Medicine ER -