{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:20:40Z","timestamp":1790824840968,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad de Buenos Aires UBACYT","award":["20020220300118BA"],"award-info":[{"award-number":["20020220300118BA"]}]},{"name":"Universidad de Buenos Aires UBACYT","award":["PUE-0017CO-2016"],"award-info":[{"award-number":["PUE-0017CO-2016"]}]},{"name":"Universidad de Buenos Aires UBACYT","award":["PIP-2021-2023 2608"],"award-info":[{"award-number":["PIP-2021-2023 2608"]}]},{"name":"Universidad de Buenos Aires UBACYT","award":["2020\u2014SERIEA-03061"],"award-info":[{"award-number":["2020\u2014SERIEA-03061"]}]},{"name":"Universidad de Buenos Aires UBACYT","award":["PICT-2018-2861"],"award-info":[{"award-number":["PICT-2018-2861"]}]},{"name":"Universidad de Buenos Aires UBACYT","award":["PICT-2019-04426"],"award-info":[{"award-number":["PICT-2019-04426"]}]},{"name":"Universidad de Buenos Aires UBACYT","award":["PICT-2021-GRF-TI-0004 04426"],"award-info":[{"award-number":["PICT-2021-GRF-TI-0004 04426"]}]},{"name":"Universidad de Buenos Aires UBACYT","award":["PPM-ANLAP-2021"],"award-info":[{"award-number":["PPM-ANLAP-2021"]}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["20020220300118BA"],"award-info":[{"award-number":["20020220300118BA"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["PUE-0017CO-2016"],"award-info":[{"award-number":["PUE-0017CO-2016"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["PIP-2021-2023 2608"],"award-info":[{"award-number":["PIP-2021-2023 2608"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["2020\u2014SERIEA-03061"],"award-info":[{"award-number":["2020\u2014SERIEA-03061"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["PICT-2018-2861"],"award-info":[{"award-number":["PICT-2018-2861"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["PICT-2019-04426"],"award-info":[{"award-number":["PICT-2019-04426"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["PICT-2021-GRF-TI-0004 04426"],"award-info":[{"award-number":["PICT-2021-GRF-TI-0004 04426"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["PPM-ANLAP-2021"],"award-info":[{"award-number":["PPM-ANLAP-2021"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007030","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica PICT","doi-asserted-by":"publisher","award":["20020220300118BA"],"award-info":[{"award-number":["20020220300118BA"]}],"id":[{"id":"10.13039\/501100007030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007030","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica PICT","doi-asserted-by":"publisher","award":["PUE-0017CO-2016"],"award-info":[{"award-number":["PUE-0017CO-2016"]}],"id":[{"id":"10.13039\/501100007030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007030","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica PICT","doi-asserted-by":"publisher","award":["PIP-2021-2023 2608"],"award-info":[{"award-number":["PIP-2021-2023 2608"]}],"id":[{"id":"10.13039\/501100007030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007030","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica PICT","doi-asserted-by":"publisher","award":["2020\u2014SERIEA-03061"],"award-info":[{"award-number":["2020\u2014SERIEA-03061"]}],"id":[{"id":"10.13039\/501100007030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007030","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica PICT","doi-asserted-by":"publisher","award":["PICT-2018-2861"],"award-info":[{"award-number":["PICT-2018-2861"]}],"id":[{"id":"10.13039\/501100007030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007030","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica PICT","doi-asserted-by":"publisher","award":["PICT-2019-04426"],"award-info":[{"award-number":["PICT-2019-04426"]}],"id":[{"id":"10.13039\/501100007030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007030","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica PICT","doi-asserted-by":"publisher","award":["PICT-2021-GRF-TI-0004 04426"],"award-info":[{"award-number":["PICT-2021-GRF-TI-0004 04426"]}],"id":[{"id":"10.13039\/501100007030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007030","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica PICT","doi-asserted-by":"publisher","award":["PPM-ANLAP-2021"],"award-info":[{"award-number":["PPM-ANLAP-2021"]}],"id":[{"id":"10.13039\/501100007030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Chagas disease, caused by the protozoan Trypanosoma cruzi, affects 6\u20137 million people worldwide. The dichloromethane extract obtained from the aerial parts of Gymnocoronis spilanthoides var subcordata showed trypanocidal activity in vitro. The fractionation of the dewaxed organic extract via column chromatography led to the isolation of three diterpenoids: ent-9\u03b1,11\u03b1-dihydroxy-15-oxo-kaur-16-en-19-oic acid or adenostemmoic acid B, (16R)-ent-11\u03b1-hydroxy-15-oxokauran-19-oic acid and ent-11\u03b1-hydroxy-15-oxo-kaur-16-en-19-oic acid. These compounds showed IC50 values of 10.6, 15.9 and 4.8 \u00b5M against T. cruzi epimastigotes, respectively. When tested against amastigotes, the diterpenoids afforded IC50 values of 6.1, 19.5 and 60.6 \u00b5M, respectively. The cytotoxicity of the compounds was tested on mammalian cells using an MTT assay, resulting in CC50s of 321.8, 23.3 and 14.8 \u00b5M, respectively. The effect of adenostemmoic acid B on T. cruzi was examined at the ultrastructural level using transmission microscopy. Treatment with 20 \u03bcM for 48 h stimulated the formation of abnormal cytosolic membranous structures in the parasite. This compound also showed an anti-inflammatory effect in murine macrophages stimulated with LPS and other TLR agonists. Treatment of macrophages with adenostemmoic acid B was able to reduce TNF secretion and nitric oxide production, while increasing IL-10 production. The combination of adenostemmoic acid B with benznidazole resulted in greater inhibition of NF-kB and a decrease in nitrite concentration. The administration of adenostemmoic acid B to mice infected with trypomastigotes of T. cruzi at the dose of 1 mg\/kg\/day for five days produced a significant decrease in parasitemia levels and weight loss. Treatment with the association with benznidazole increased the survival time of the animals. In view of these results, adenostemmoic acid B could be considered a promising candidate for further studies in the search for new treatments for Chagas disease.<\/jats:p>","DOI":"10.3390\/pharmaceutics16030415","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T06:58:39Z","timestamp":1710745119000},"page":"415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Trypanocidal and Anti-Inflammatory Effects of Three ent-Kaurane Diterpenoids from Gymnocoronis spilanthoides var. subcordata (Asteraceae)"],"prefix":"10.3390","volume":"16","author":[{"given":"Mariana G.","family":"Selener","sequence":"first","affiliation":[{"name":"C\u00e1tedra de Farmacognosia, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Jun\u00edn 956, Piso 2, Buenos Aires C1113AAD, Argentina"},{"name":"Instituto de Qu\u00edmica y Metabolismo del F\u00e1rmaco (IQUIMEFA), CONICET-Universidad de Buenos Aires, Jun\u00edn 956, Piso 2, Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimena","family":"Borgo","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Farmacognosia, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Jun\u00edn 956, Piso 2, Buenos Aires C1113AAD, Argentina"},{"name":"Instituto de Qu\u00edmica y Metabolismo del F\u00e1rmaco (IQUIMEFA), CONICET-Universidad de Buenos Aires, Jun\u00edn 956, Piso 2, Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2144-7835","authenticated-orcid":false,"given":"Maria Belen","family":"Sarratea","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-Universidad de Buenos Aires, Jun\u00edn 956, Piso 4, Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Alicia","family":"Delfino","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Inmunolog\u00eda, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Jun\u00edn 956, Piso 4, Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C.","family":"Laurella","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Farmacognosia, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Jun\u00edn 956, Piso 2, Buenos Aires C1113AAD, Argentina"},{"name":"Instituto de Qu\u00edmica y Metabolismo del F\u00e1rmaco (IQUIMEFA), CONICET-Universidad de Buenos Aires, Jun\u00edn 956, Piso 2, Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natacha","family":"Cerny","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda, Parasitolog\u00eda e Inmunolog\u00eda-IMPAM (UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires C1121ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Gomez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias M\u00e9dicas, Instituto de Histolog\u00eda y Embriolog\u00eda \u201cDr. Mario H. Burgos\u201d (IHEM), Universidad Nacional de Cuyo-CONICET, CC 56, Mendoza 5500, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Coll","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias M\u00e9dicas, Instituto de Histolog\u00eda y Embriolog\u00eda \u201cDr. Mario H. Burgos\u201d (IHEM), Universidad Nacional de Cuyo-CONICET, CC 56, Mendoza 5500, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7501-3330","authenticated-orcid":false,"given":"Emilio L.","family":"Malchiodi","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-Universidad de Buenos Aires, Jun\u00edn 956, Piso 4, Buenos Aires C1113AAD, Argentina"},{"name":"C\u00e1tedra de Inmunolog\u00eda, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Jun\u00edn 956, Piso 4, Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0520-0226","authenticated-orcid":false,"given":"Augusto E.","family":"Bivona","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-Universidad de Buenos Aires, Jun\u00edn 956, Piso 4, Buenos Aires C1113AAD, Argentina"},{"name":"C\u00e1tedra de Inmunolog\u00eda, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Jun\u00edn 956, Piso 4, Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Barrera","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias M\u00e9dicas, Instituto de Histolog\u00eda y Embriolog\u00eda \u201cDr. Mario H. Burgos\u201d (IHEM), Universidad Nacional de Cuyo-CONICET, CC 56, Mendoza 5500, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0653-4850","authenticated-orcid":false,"given":"Flavia C.","family":"Redko","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Farmacognosia, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Jun\u00edn 956, Piso 2, Buenos Aires C1113AAD, Argentina"},{"name":"Instituto de Qu\u00edmica y Metabolismo del F\u00e1rmaco (IQUIMEFA), CONICET-Universidad de Buenos Aires, Jun\u00edn 956, Piso 2, Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar A. N.","family":"Catal\u00e1n","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica Org\u00e1nica, Facultad de Bioqu\u00edmica, Qu\u00edmica y Farmacia, Universidad Nacional de Tucum\u00e1n, Ayacucho 471, San Miguel de Tucum\u00e1n T4000INI, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5369-2889","authenticated-orcid":false,"given":"Andr\u00e9s S\u00e1nchez","family":"Alberti","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-Universidad de Buenos Aires, Jun\u00edn 956, Piso 4, Buenos Aires C1113AAD, Argentina"},{"name":"Departamento de Microbiolog\u00eda, Parasitolog\u00eda e Inmunolog\u00eda-IMPAM (UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires C1121ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9322-5748","authenticated-orcid":false,"given":"Valeria P.","family":"S\u00fclsen","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Farmacognosia, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Jun\u00edn 956, Piso 2, Buenos Aires C1113AAD, Argentina"},{"name":"Instituto de Qu\u00edmica y Metabolismo del F\u00e1rmaco (IQUIMEFA), CONICET-Universidad de Buenos Aires, Jun\u00edn 956, Piso 2, Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"ref_1","unstructured":"(2023, July 12). La Enfermedad de Chagas (Tripanosomiasis Americana). Available online: https:\/\/www.who.int\/es\/news-room\/fact-sheets\/detail\/chagas-disease-(american-trypanosomiasis)."},{"key":"ref_2","unstructured":"PAHO\/WHO|Pan American Health Organization (2023, November 22). Chagas Disease, Available online: https:\/\/www.paho.org\/en\/topics\/chagas-disease."},{"key":"ref_3","unstructured":"Ryan, E.T., Hill, D.R., Solomon, T., Aronson, N.E., and Endy, T.P. (2020). Hunter\u2019s Tropical Medicine and Emerging Infectious Diseases, Elsevier. [10th ed.]."},{"key":"ref_4","unstructured":"CDC-DPDx (2024, February 11). American Trypanosomiasis, Available online: https:\/\/www.cdc.gov\/dpdx\/trypanosomiasisamerican\/index.html."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1056\/NEJMoa1507574","article-title":"Randomized Trial of Benznidazole for Chronic Chagas\u2019 Cardiomyopathy","volume":"373","author":"Morillo","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Pecoul, B., Batista, C., Stobbaerts, E., Ribeiro, I., Vilasanjuan, R., Gascon, J., Pinazo, M.J., Moriana, S., Gold, S., and Pereiro, A. (2016). The BENEFIT Trial: Where Do We Go from Here?. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004343"},{"key":"ref_7","unstructured":"DNDi Am\u00e9rica Latina (2023, November 22). Enfermedad de Chagas. Available online: https:\/\/dndial.org\/es\/doencas\/doenca-de-chagas\/."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gravina, H.D., Antonelli, L., Gazzinelli, R.T., and Ropert, C. (2013). Differential Use of TLR2 and TLR9 in the Regulation of Immune Responses during the Infection with Trypanosoma cruzi. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063100"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.molmed.2007.09.002","article-title":"Signaling to NF-\u03baB by Toll-like Receptors","volume":"13","author":"Kawai","year":"2007","journal-title":"Trends Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.tcm.2016.08.003","article-title":"Molecular Mechanisms of Cardiac Electromechanical Remodeling during Chagas Disease: Role of TNF and TGF-\u03b2","volume":"27","author":"Cruz","year":"2017","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"946350","DOI":"10.3389\/fimmu.2022.946350","article-title":"Interleukin 10 Polymorphisms as Risk Factors for Progression to Chagas Disease Cardiomyopathy: A Case-Control Study and Meta-Analysis","volume":"13","author":"Grijalva","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rolski, F., and B\u0142yszczuk, P. (2020). Complexity of TNF-\u03b1 Signaling in Heart Disease. J. Clin. Med., 9.","DOI":"10.3390\/jcm9103267"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s13237-022-00405-3","article-title":"Plant-Derived Natural Products for Drug Discovery: Current Approaches and Prospects","volume":"65","author":"Nasim","year":"2022","journal-title":"Nucleus"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2174\/1568026623666221212111514","article-title":"The Potential of Secondary Metabolites from Plants as Drugs or Leads against Trypanosoma cruzi\u2014An Update from 2012 to 2021","volume":"23","author":"Barbosa","year":"2023","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1177\/1087057114550585","article-title":"Chagas Disease Drug Discovery: Toward a New Era","volume":"20","author":"Chatelain","year":"2015","journal-title":"SLAS Discov."},{"key":"ref_16","unstructured":"Hurrell, J., Bazzano, D., and Delucchi, G. (2006). Biota Rioplatense. Volumen XI. Dicotiledoneas Herb\u00e1ceas 1. Nativas y Ex\u00f3ticas, Editorial L.O.L.A. (Literature of Latin Am\u00e9rica)."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/pca.2555","article-title":"Recognition of Pyrrolizidine Alkaloid Esters in the Invasive Aquatic Plant Gymnocoronis spilanthoides (Asteraceae)","volume":"26","author":"Colegate","year":"2015","journal-title":"Phytochem. Anal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3372\/wi.46.46208","article-title":"Gymnocoronis spilanthoides (Asteraceae, Eupatorieae), a New Naturalized and Potentially Invasive Aquatic Alien in S Europe","volume":"46","author":"Ardenghi","year":"2016","journal-title":"Willdenowia"},{"key":"ref_19","first-page":"1854","article-title":"Anti-Trypanosoma cruzi Activity of Extracts from Argentinean Asteraceae Species","volume":"18","author":"Selener","year":"2019","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e6622894","DOI":"10.1155\/2021\/6622894","article-title":"Antiprotozoal Compounds from Urolepis hecatantha (Asteraceae)","volume":"2021","author":"Elso","year":"2021","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Borgo, J., Elso, O.G., Gomez, J., Coll, M., Catal\u00e1n, C.A.N., Mucci, J., Alvarez, G., Randall, L.M., Barrera, P., and Malchiodi, E.L. (2023). Anti-Trypanosoma cruzi Properties of Sesquiterpene Lactones Isolated from Stevia spp.: In Vitro and In Silico Studies. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020647"},{"key":"ref_22","first-page":"557","article-title":"In Vitro Antiprotozoal Activity and Chemical Composition of Ambrosia Tenuifolia and A. Scabra Essential Oils","volume":"3","author":"Cazorla","year":"2008","journal-title":"Nat. Prod. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1021\/acsomega.1c05560","article-title":"In Vitro, In Vivo, and In Silico Studies of Cumanin Diacetate as a Potential Drug against Trypanosoma cruzi Infection","volume":"7","author":"Beer","year":"2022","journal-title":"ACS Omega"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1645\/0022-3395(2000)086[0407:TSLDDA]2.0.CO;2","article-title":"The sesquiterpene lactone dehydroleucodine (DhL) affects the growth of cultured epimastigotes of Trypanosoma cruzi","volume":"86","author":"Brengio","year":"2000","journal-title":"J. Parasitol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.ijantimicag.2011.02.003","article-title":"Psilostachyin C: A Natural Compound with Trypanocidal Activity","volume":"37","author":"Frank","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_26","unstructured":"(2023, November 21). RAW-LuciaTM ISG Cells. Available online: https:\/\/www.invivogen.com\/raw-lucia-isg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3390\/s30800276","article-title":"Measurement of Nitric Oxide Production in Biological Systems by Using Griess Reaction Assay","volume":"3","author":"Sun","year":"2003","journal-title":"Sensors"},{"key":"ref_28","unstructured":"Institute of Laboratory Animal Resources (US), and Committee on Care and Use of Laboratory Animals (2010). Guide for the Care and Use of Laboratory Animals: Eighth Edition, National Academies Press."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1248\/cpb.38.1308","article-title":"Kaurane-Type Diterpenes from Adenostemma Lavenia O. Kuntze","volume":"38","author":"Shimizu","year":"1990","journal-title":"Chem. Pharm. Bull."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1021\/jo00868a023","article-title":"New Hydroxylated Ent-Kauranoic Acids from Eupatorium Album","volume":"41","author":"Herz","year":"1976","journal-title":"J. Org. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1016\/j.molimm.2010.06.002","article-title":"Benznidazole Blocks NF-\u03baB Activation but Not AP-1 through Inhibition of IKK","volume":"47","author":"Manarin","year":"2010","journal-title":"Mol. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8488","DOI":"10.3390\/molecules19068488","article-title":"In Vivo Anti-Trypanosoma cruzi Activity of Hydro-Ethanolic Extract and Isolated Active Principles from Aristeguietia glutinosa and Mechanism of Action Studies","volume":"19","author":"Varela","year":"2014","journal-title":"Molecules"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/S0031-9422(00)94244-4","article-title":"Kaurenic Acid Derivatives from Adenostemma caffrum","volume":"17","author":"Bohlmann","year":"1978","journal-title":"Phytochemistry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1021\/np50002a009","article-title":"Isolation of 11-Hydroxyated Kauranic Acids from Adenostemma lavenia","volume":"42","author":"Cheng","year":"1979","journal-title":"J. Nat. Prod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1080\/14786419.2015.1126260","article-title":"Active Sesquiterpene Lactones against Leishmania amazonensis and Leishmania braziliensis","volume":"30","author":"Sosa","year":"2016","journal-title":"Nat. Prod. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3944","DOI":"10.1021\/acs.jmedchem.5b00208","article-title":"Ent-Kaurane Diterpenoids from Chinese Liverworts and Their Antitumor Activities through Michael Addition as Detected In Situ by a Fluorescence Probe","volume":"58","author":"Lin","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/ptr.5749","article-title":"Diterpenes as Lead Molecules against Neglected Tropical Diseases","volume":"31","author":"Rolim","year":"2017","journal-title":"Phytother. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1021\/jm201451h","article-title":"Terpenes from Copaifera Demonstrated In Vitro Antiparasitic and Synergic Activity","volume":"55","author":"Izumi","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41419-019-1370-2","article-title":"Cell Death Pathways in Pathogenic Trypanosomatids: Lessons of (over)Kill","volume":"10","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"De Souza, W. (2002). From the Cell Biology to the Development of New Chemotherapeutic Approaches against Trypanosomatids: Dreams and Reality. Kinetoplastid Biol. Dis., 1.","DOI":"10.1186\/1475-9292-1-3"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cytogfr.2021.10.001","article-title":"Chagas Disease: Immunology of the Disease at a Glance","volume":"62","author":"Hernandes","year":"2021","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1244071","DOI":"10.3389\/fimmu.2023.1244071","article-title":"Immunopathogenesis in Trypanosoma cruzi Infection: A Role for Suppressed Macrophages and Apoptotic Cells","volume":"14","author":"Vellozo","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1128\/IAI.01176-10","article-title":"Type I Interferons Increase Host Susceptibility to Trypanosoma cruzi Infection","volume":"79","author":"Chessler","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"638020","DOI":"10.3389\/fimmu.2021.638020","article-title":"The First Contact of Human Dendritic Cells with Trypanosoma cruzi Reveals Response to Virus as an Unexplored Central Pathway","volume":"12","author":"Rocha","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_45","first-page":"1","article-title":"The Medicinal Potential of Plants from the Adenostemma genus","volume":"13","author":"Nurlela","year":"2023","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1590\/S0074-02762009000800004","article-title":"Gap Junction Reduction in Cardiomyocytes Following Transforming Growth Factor-\u03b2 Treatment and Trypanosoma cruzi Infection","volume":"104","author":"Waghabi","year":"2009","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Santos, E.d.S., Silva, D.K.C., dos Reis, B.P.Z.C., Barreto, B.C., Cardoso, C.M.A., Ribeiro dos Santos, R., Meira, C.S., and Soares, M.B.P. (2021). Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.765879"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e507874","DOI":"10.1155\/2012\/507874","article-title":"The Immune Response to Trypanosoma cruzi: Role of Toll-Like Receptors and Perspectives for Vaccine Development","volume":"2012","author":"Rodrigues","year":"2012","journal-title":"J. Parasitol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1111\/sji.12501","article-title":"Participation of TLR2 and TLR4 in Cytokines Production by Patients with Symptomatic and Asymptomatic Chronic Chagas Disease","volume":"85","author":"Gatto","year":"2017","journal-title":"Scand. J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e12769","DOI":"10.1111\/pim.12769","article-title":"TLR4 Agonist Protects against Trypanosoma cruzi Acute Lethal Infection by Decreasing Cardiac Parasite Burdens","volume":"42","author":"Versteeg","year":"2020","journal-title":"Parasite Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e711","DOI":"10.1016\/S2666-5247(21)00265-2","article-title":"Pathogen Diversity, Immunity, and the Fate of Infections: Lessons Learned from Trypanosoma cruzi Human\u2013Host Interactions","volume":"3","author":"Gollob","year":"2022","journal-title":"Lancet Microbe"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/3\/415\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:15:12Z","timestamp":1760105712000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/3\/415"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,18]]},"references-count":51,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["pharmaceutics16030415"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16030415","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,18]]}}}