Short Communications | Published:

DOI: 10.1007/s42535-024-00948-7
First Page: 1261
Last Page: 1266
Views: 1957

Keywords: n Tocoyena formosan , Antiparasitário, Citotoxicidade


Abstract


Chagas disease and leishmaniasis are considered severe public health problems and are part of the group of neglected tropical diseases. To find new therapeutic agents for these diseases, researchers evaluated the antiparasitic activity and cytotoxic potential of a hydroethanolic extract from the leaves of Tocoyena formosa (Cham. & Schlecht.) K. Schum (EHFTF). The antiparasitic evaluation of EHFTF was conducted at concentrations of 250, 500, and 1000 µg/mL in vitro, using CL-B5 clones (T. cruzi) and cultures of Leishmania spp. For the cytotoxicity test, fibroblasts were used. Statistical analysis was performed using the regression method. The results showed that EHFTF exhibited low toxicity at the maximum tested concentration of 1000 µg/mL. EHFTF demonstrated antiparasitic activity, particularly against species of Leishmania. Specifically, at a concentration of 1000 µg/mL, the extract inhibited 11.94% of the epimastigote form of T. cruzi, 71.52% of the promastigote form of L. infantum, and 35.04% of the promastigote form of L. braziliensis. At a concentration of 500 µg/mL, the extract inhibited 10.02% of the promastigote form of L. braziliensis, but did not show significant reduction against T. cruzi and L. infantum. The cytotoxicity test on fibroblasts revealed that EHFTF exhibited low toxicity even at the maximum concentration. In conclusion, EHFTF demonstrated antiparasitic activity against L. infantum and showed low cytotoxicity to fibroblasts.



References


Alcântara LM, Ferreira TCS, Gadelha FR, Miguel DC (2018) Challenges in drug discovery targeting TriTryp diseases with an emphasis on leishmaniasis. Int J Parasitol Drugs Drug Resist 8:430–439. https://doi.org/10.1016/j.ijpddr.2018.09.006


Andrade JC, da Silva ARP, dos Santos ATL, Freitas MA, de Matos YMLS, Braga MFBM, Bezerra CF, Gonçalo MIP, Gomez MCV, Rolóm M (2019) Chemical composition, antiparasitic and cytotoxic activities of aqueous extracts of Ziziphus Joazeiro Mart. Asian Pac J Trop Biomed 9:222. https://doi.org/10.4103/2221-1691.259003


Boeck P, Falcao CAB, Leal PC, Yunes RA, Cechinel Filho V, Torres-Santos EC, Rossi-Bergmann B (2006) Synthesis of chalcone analogues with increased antileishmanial activity. Bioorg Med Chem 14:1538–1545. https://doi.org/10.1016/j.bmc.2005.10.005


Carothers S, Nyamwihura R, Collins J, Zhang H, Park H, Setzer WN, Ogungbe IV (2018) Bauerenol acetate, the pentacyclic triterpenoid from Tabernaemontana longipes, is an antitrypanosomal agent. Molecules 23:355. https://doi.org/10.3390/molecules23020355


Cesário FRAS, de Albuquerque TR, da Silva BAF, de Lacerda GM, Rodrigues LB, Martins AOBPB, Quintans-Júnior LJ, da Silva Almeida JRG, Vale ML, Coutinho HDM (2018a) Evaluation of the antioxidant and gastroprotective activity and HPLC analysis of the hydroalcoholic extract of Tocoyena formosa leaves (Cham. & Schlecht) K. Schum. Food Chem Toxicol 112:355–362. https://doi.org/10.1016/j.fct.2017.12.058


Cesário FRAS, de Albuquerque TR, de Lacerda GM, de Oliveira MRC, Rodrigues LB, Martins AOBPB, Boligon AA, Júnior LJQ, de Souza Araújo AA, Vale ML (2018b) Phytochemical profile and mechanisms involved in the anti-nociception caused by the hydroethanolic extract obtained from Tocoyena formosa (Cham. & Schltdl.) K. Schum (Jenipapo-bravo) leaves in mice. Biomed Pharmacother 97: 321–329. https://doi.org/10.1016/j.biopha.2017.10.054


Cesário FRAS, de Albuquerque TR, de Lacerda GM, de Oliveira MRC, da Silva BAF, Rodrigues LB, Martins AOBPB, da Silva Almeida JRG, Vale ML, Coutinho HDM (2019) Chemical fingerprint, acute oral toxicity and anti-inflammatory activity of the hydroalcoholic extract of leaves from Tocoyena formosa (Cham. & Schlecht.) K. Schum. Saudi J Biol Sci 26:873–880. https://doi.org/10.1016/j.sjbs.2018.01.008


Chandrasekar R, Debnath S, Sivagami B (2018) Therapeutic efficacy of flavonoids and terpenoids an ongoing herbal therapy in the Treatment of Leishmaniasis. Nat Prod Ind J 14(2):124


Chaves JO, De Souza MC, Da Silva LC, Lachos-Perez D, Torres-Mayanga PC, Machado APDF, Forster-Carneiro T, Vázquez-Espinosa M, González-de-Peredo AV, Barbero GF (2020) Extraction of flavonoids from natural sources using modern techniques. Front Chem 8:507887. https://doi.org/10.3389/fchem.2020.507887


Choi HL, Jain S, Ruiz Postigo JA, Borisch B, Dagne DA (2021) The global procurement landscape of leishmaniasis medicines. Deye G (Ed.). PLoS Negl Trop Dis 15: e0009181. https://doi.org/10.1371/journal.pntd.0009181


Citadini-Zanette V, Della Colle MP, Pereira RC, Rossato AE, Ferreira MEA, dos Santos R (2017) Fitoterapia Racional: aspectos taxonômicos, agroecológicos, etnobotânicos e terapêuticos. Unisanta BioScience 6:8–13. https://periodicos.unisanta.br/index.php/bio/article/view/967/905


Correia VC, de Lima S, Oliveira NO, de Santos FA, de Teles AP, de Oliveira Júnior CBG (2016) Evaluation of the antiplasmodial and leishmanicidal potential of Myrciaria dubia (Myrtaceae) extract. Rev Soc Bras Med Trop 49: 586–592. https://doi.org/10.1590/0037-8682-0227-2016


Ferreira LLG, Andricopulo AD (2020) World Chagas Disease Day and the New Road Map for Neglected Tropical diseases. Curr Top Med Chem 20:1518–1520. https://doi.org/10.2174/156802662017200624115305


Ferreira RTB, Branquinho MR, Leite PC (2014) Transmissão oral da doença de Chagas pelo consumo de açaí: um desafio para a Vigilância Sanitária. Vig Sanit Debate 2(04):4. https://doi.org/1110.3395/VD.V2i4.358


Fonseca B, de Albuquerque P, Zicker PC F (2020) Neglected tropical diseases in Brazil: lack of correlation between disease burden, research funding and output. Trop Med Int Health 25:1373–1384. https://doi.org/10.1016/10.1111/tmi.13478


García-Huertas P, Cardona-Castro N (2021) Advances in the treatment of Chagas disease: promising new drugs, plants and targets. Biomed Pharmacother 142:112020. https://doi.org/10.1016/j.biopha.2021.112020


Gervazoni LFO, Barcellos GB, Ferreira-Paes T, Almeida-Amaral EE (2020) Use of Natural products in Leishmaniasis Chemotherapy: an overview. Front Chem 23:8579891. https://doi.org/10.3389/fchem.2020.579891


Hotez PJ, Lo NC (2020) Neglected Tropical diseases. In: Ryan ET, Solomon T, Endy TP, Hill DR, Aronson NE (eds) Hunter’s Tropical Medicine and Emerging Infectious diseases. Elsevier, pp 209–213. https://doi.org/10.1016/B978-0-323-55512-8.00027-2





Jesus JA, Lago JHG, Laurenti MD, Yamamoto ES, Passero LFD (2015) Antimicrobial activity of oleanolic and ursolic acids: an update. Evid Based Complement Alternat Med 2015:620472. https://doi.org/10.1155/2015/620472


Kolodziej H, Kiderlen AF (2005) Antileishmanial activity and immune modulatory effects of tannins and related compounds on Leishmania parasitised RAW 264.7 cells. Phytochemistry 66:2056–2071. https://doi.org/10.1016/j.phytochem.2005.01.011


Lefebvre T, Destandau E, Lesellier E (2020) Selective extraction of bioactive compounds from plants using recent extraction techniques: a review. J Chromatogr A 461770. https://doi.org/10.1016/j.chroma.2020.461770


Le-Senne A, Muelas-Serrano S, Fernández-Portillo C, Escario JA, Gómez-Barrio A (2002) Biological characterization of a beta-galactosidase expressing clone of Trypanosoma Cruzi CL strain. Mem Inst Oswaldo Cruz 97:1101–1105. https://doi.org/10.1590/S0074-02762002000800006


Lima TC, Souza R, de Moraes J, de Steindel MH, Biavatti M MW (2016) A New Furanoheliangolide Sesquiterpene Lactone from Calea Pinnatifida (R. Br.) Less. (Asteraceae) and evaluation of its Trypanocidal and Leishmanicidal activities. J Braz Chem Soc 28:367–375. https://doi.org/10.5935/0103-5053.20160186


Salas M, B Caballero J, Esteban-Parra AM, Mendez-Arriaga GM J (2017) Leishmanicidal and Trypanocidal Activity of Metal Complexes with 1, 2, 4-Triazolo [1, 5-a] pyrimidines: insights on their therapeutic potential against Leishmaniasis and Chagas Disease. Curr Med Chem 24:2796–2806. https://doi.org/10.2174/0929867324666170516122024


Malecela MN, Ducker C (2021) A road map for neglected tropical diseases 2021–2030. Trans R Soc Trop Med Hyg 115:121–123. https://doi.org/10.1093/trstmh/trab002


Matsuda CN, Cardoso J, Dantas AG, Barretto ACP (2014) Doença De Chagas. RBM rev bras med 71:347–353


Muganza DM, Fruth BI, Lami JN, Cos P, Kanyanga RC, Maes L, Pieters L (2015) In vitro antiprotozoal activity and cytotoxicity of extracts and fractions from the leaves, root bark and stem bark of Isolona hexaloba. J Ethnopharmacol 174:187–194. https://doi.org/10.1016/j.jep.2015.07.034


Nardella F, Gallé J-B, Bourjot M, Weniger B, Vonthron-Sénécheau C (2018) Antileishmanial and Antitrypanosomal activities of flavonoids. Nat Antimicrob Agents 163–194. https://doi.org/10.1007/978-3-319-67045-4_7


Nawaz H, Shad MA, Rehman N, Andaleeb H, Ullah N (2020) Effect of solvent polarity on extraction yield and antioxidant properties of phytochemicals from bean (Phaseolus vulgaris) seeds. RBCF 56:e17129. https://doi.org/10.1590/s2175-97902019000417129


Ortiz OGP, Rozo AM (2016) Leishmaniasis: Nuevos Tratamientos, Mecanismos De Acción Y Sus Implicaciones. Rev Cient del Depart de Medic 1: 22–30.


Palmer-Young EC, Sadd BM, Irwin RE, Adler LS (2017) Synergistic effects of floral phytochemicals against a bumble bee parasite. Ecol Evol 7:1836–1849. https://doi.org/10.1002/ece3.2794


Roldos V, Nakayama H, Rolón M, Montero-Torres A, Trucco F, Torres S, Vega C, Marrero-Ponce Y, Heguaburu V, Yaluff G (2008) Activity of a hydroxybibenzyl bryophyte constituent against Leishmania spp. and Trypanosoma Cruzi: in silico, in vitro and in vivo activity studies. Eur J Med Chem 43:1797–1807. https://doi.org/10.1016/j.ejmech.2007.11.007


Rolón M, Seco EM, Vega C, Nogal JJ, Escario JA, Gómez-Barrio A, Malpartida F (2006) Selective activity of polyene macrolides produced by genetically modified Streptomyces on Trypanosoma Cruzi. Int J Antimicrob Agents 28:104–109. https://doi.org/10.1016/j.ijantimicag.2006.02.025


Rosas LV, Cordeiro MSC, Campos FR, Nascimento SKR, Januário AH, França SC, Nomizo A, Toldo MPA, Albuquerque S, Pereira PS (2007) In vitro evaluation of the cytotoxic and trypanocidal activities of Ampelozizyphus amazonicus (Rhamnaceae). Braz J Med Biol Res 40:663–670. https://doi.org/10.1590/S0100-879X2007000500009


Sá JC, Almeida-Souza F, Mondêgo-Oliveira R, da Silva Oliveira I dos, Lamarck S, Magalhães L, de FB I, Ataídes-Lima AF, da Silva Ferreira H, Abreu-Silva AL (2015) Leishmanicidal, cytotoxicity and wound healing potential of Arrabidaea chica Verlot. BMC Complement Altern Med 16: 1–11. https://doi.org/10.1186/s12906-015-0973-0


Sangshetti JN, Khan FAK, Kulkarni AA, Arote R, Patil RH (2015) Antileishmanial drug discovery: comprehensive review of the last 10 years. RSC Adv 5:32376–32415. https://doi.org/10.1039/C5RA02669E


Santos FM, Malafaia CA, Simas DLR, Paulino AB, Muzitano MF, Simas NK, Cruz Da-Rocha EA, Amaral ACF, Leal ICR (2020a) Phenolic compounds from Tocoyena bullata Mart (Rubiaceae) with inhibitory activity in mast cells degranulation. Nat Prod Res 34:3295–3298. https://doi.org/10.1080/14786419.2018.1560281


Sales VS, Monteiro ÁB, de Araújo Delmondes G, do Nascimento EP (2018) Antiparasitic activity and essential oil chemical analysis of the Piper tuberculatum Jacq fruit. Iran J Pharm Res 17:268–275 PMCID: PMC5937097


Santos SS, de Araújo RV, Giarolla J, Seoud O, El, Ferreira EI (2020b) Searching for drugs for Chagas disease, leishmaniasis and schistosomiasis: a review. Int J Antimicrob Agents 55:105906. https://doi.org/10.1016/j.ijantimicag.2020.105906


Silva Af R, Mfr E, Mm (2015) Angiosperm diversity and medicinal species of Cerrado area. Rev Bras Plantas Med 17:1016–1030. https://doi.org/10.1590/1983-084X/14_115


Silva MA, da Silva GA, Marques MJ, Bastos RG, da Silva AF, Rosa CP, Espuri PF (2017) Triagem fitoquímica, atividade antioxidante e leishmanicida do extrato hidroetanólico 70%(v/v) e das frações obtidas de (Annona Crassiflora Mart). Revista Fitos 10:505–517. https://doi.org/10.5935/2446-4775.20160036


Silva ML, Sales FS, Levatti EVC, Antar GM, Tempone AG, Lago JHG, Jerz G (2023) Evaluation of Anti-trypanosoma Cruzi activity of Chemical constituents from Baccharis sphenophylla isolated using high-performance countercurrent chromatography. Molecules 29:212. https://doi.org/10.3390/molecules29010212


Sousa E, Rosa A, Santos R, Santos I, Sousa V, Carvalho F, Júnior G, Chaves M (2018) Composição química E atividade antileishmania de tocoyena hispidula. Quim Nova 42(2):192–196. https://doi.org/10.21577/0100-4042.20170313


Souza AMT, Castro HC, Brito MA, Andrighetti-Fröhner CR, Magalhaes U, Oliveira KN, Gaspar-Silva D, Pacheco LK, Joussef AC, Steindel M (2009) Leishmania amazonensis growth inhibitors: biological and theoretical features of sulfonamide 4-methoxychalcone derivatives. Curr Microbiol 59:374–379. https://doi.org/10.1007/s00284-009-9447-2


Steiger SN, Elshaboury RH, Gandhi RG (2020a) Benznidazole. Hunter’s Tropical Medicine and Emerging Infectious diseases. Elsevier, pp 1147–1148. https://doi.org/10.1016/B978-0-323-55512-8.00164-2


Steiger SN, Elshaboury RH, Gandhi RG (2020b) Nifurtimox. Hunter’s Tropical Medicine and Emerging Infectious diseases. Elsevier, pp 1161–1162. https://doi.org/10.1016/B978-0-323-55512-8.00171-X


Tasdemir D, Kaiser M, Brun R, Yardley V, Schmidt TJ, Tosun F, Rüedi P (2006) Antitrypanosomal and antileishmanial activities of flavonoids and their analogues: in vitro, in vivo, structure-activity relationship, and quantitative structure-activity relationship studies. Antimicrob Agents Chemother 50:1352–1364. https://doi.org/10.1128/AAC.50.4.1352-1364.2006


Valle-Reyes JS, Melnikov V, Dobrovinskaya O, Rodriguez-Hernández A, Wookee-Zea C, Pimientel-Rodrigez V, Rueda-Valdovinos G, Delgado-Enciso I, López-Lemus UA, Espinoza-Gómez F (2017) Antiprotozoal drug nitazoxanide enhances parasitemia, tissue lesions and mortality caused by Trypanosoma Cruzi in murine model. Exp Parasitol 172:44–50. https://doi.org/10.1016/j.exppara.2016.12.013


Vandesmet VCS, Felipe CFB, Kerntopf MR, Rolón M, Vega C, Coronel C, Barbosa AGR, Coutinho HDM, Menezes IRA (2017) The use of herbs against neglected diseases: evaluation of in vitro leishmanicidal and trypanocidal activity of Stryphnodendron Rotundifolium Mart. Saudi J Biol Sci 24:1136–1141. https://doi.org/10.1016/j.sjbs.2015.03.001

 


Author Information


Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri, Pimenta, Crato, Brazil