Abstract
Leishmania infantum is an etiologic agent of visceral leishmaniasis. This disease is a neglected disease that can be fatal if not treated and additionally, the few therapeutic option present several drawbacks, including difficult route of administration and toxicity, which turn the search for new therapeutic alternatives necessary. Herein, we evaluated the leishmanicidal in vitro activity of the solanum extract from Solanum lycocarpum A. St.-Hil., Solanaceae, and the isolated alkaloids solasodine, solamargine and solasonine against promastigotes and intracellular amastigotes of L. infantum. Solasodine (IC50-pro = 4.7 μg/ml; IC50-ama = 10.8 μg/ml) and solamargine (IC50-pro = 8.1 μg/ml; IC50-ama = 3.0 μg/ml) exhibited interesting leishmanicidal ativity. Solasonine was approximately four-times (Selective Index 3.7) more selective to the parasite than to the host cells. This data suggest that solasonine might be considered as a potential drug candidate for leishmaniasis treatment.
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Abdel-Sattar, E., Maes, L., Salama, M.M., 2010. In vitro activities of plant extracts from Saudi Arabia against malaria, leishmaniasis, sleeping sickness and Chagas disease. Phytother. Res. 24, 1322–1328.
Balasubramanian, G., Sarathi, M., Kumar, S.R., Hameed, A.S.S., 2007. Screening the antiviral activity of Indian medicinal plants against white spot syndrome virus in shrimp. Aquaculture 263, 15–19.
Bekele, B., Adane, L., Tariku, Y., Hailu, A., 2013. Evaluation of antileishmanial activities of triglycerides isolated from roots of Moringa stenopetala. Med. Chem. Res. 22, 4592–4599.
Cham, B.E., Daunter, B., 1990. Solasodine glycosides. Selective cytotoxicity for cancer cells and inhibition of cytotoxicity by rhamnose in mice with sarcoma 180. Cancer Lett. 55, 221–225.
Chung, M.C., Ferreira, E.I., Santos, J.L., Giarolla, J., Rando, D.G., Almeida, A.E., Bosquesi, P.L., Menegon, R.F., Blau, L., 2007. Prodrugs for the treatment of neglected diseases. Molecules 13, 616–677.
Coqueiro, A., Regasini, L.O., Leme, G.M., Polese, L., Nogueira, C.T., Cistia, M.L., Gram-inha, M.A.S., Bolzani, V.S., 2014. Leishmanicidal activity of Brosimum glaziovii (Moraceae) and chemical composition of the bioactive fractions by using High-Resolution Gas Chromatography and GC-MS. J. Braz. Chem. Soc. 25, 1839–1847.
Croft, S.L., Sundar, S., Fairlamb, A.H., 2006. Drug resistance in leishmaniasis. Clin. Microbiol. Rev. 19, 111–126.
Cruz, G.L.A., Silva, C., 1995. Dicionário De Plantas úteis do Brasil. Bertrand, Rio de Janeiro.
Dall’Agnol, R., Von Poser, G.L., 2000. The use of complex polysaccharides in the management of metabolic diseases: the case of Solanum lycocarpum fruits. J. Ethnopharmacol. 71, 337–341.
De Almeida, L., Passalacqua, T.G., Dutra, L.A., Fonseca, J.N.V.D., Nascimento, R.F.Q., Imamura, K.B., de Andrade, C.R., Dos Santos, J.L., Graminha, M.A.S., 2017. In vivo antileishmanial activity and histopathological evaluation in Leishmania infantum infected hamsters after treatment with a furoxan derivative. Biomed. Pharmacother. 95, 536–547.
Devkota, K.P., Choudhary, M.I., Ranjit, R., Samreen, Sewald, N., 2007. Structure activity relationship studies on antileishmanial steroidal alkaloids from Sarcococca hookeriana. Nat. Prod. Res. 21, 292–297.
Dutra, L.A., de Almeida, L., Passalacqua, T.G., Reis, J.S., Torres, F.A., Martinez, I., Peccinini, R.G., Chin, C.M., Chegaev, K., Guglielmo, S., Fruttero, R., Graminha, M.A.S., dos Santos, J.L., 2014. Leishmanicidal activities of novel synthetic furoxan and benzofuroxan derivatives. Antimicrob. Agents Chemother. 58, 4837–4847.
Estevez, Y., Castillo, D., Tangoa Pisango, M., Arevalo, J., Rojas, R., Alban, J., Deharo, E., Bourdy, G., Sauvain, M., 2007. Evaluation of the leishmanicidal activity of plants used by Peruvian Chayahuita ethnic group. J. Ethnopharmacol. 114, 254–259.
Fewell, A.M., Roddick, J.G., Weissenberg, M., 1994. Interactions between the glycoalkaloids solasonine and solamargine in relation to inhibition of fungal growth. Phytochemistry 37, 1007–1011.
Filho, V.C., Meyre-Silva, C., Niero, R., Bolda Mariano, L.N., Gomes do Nascimento, F., Vicente Farias, I., Gazoni, V.F., Dos Santos Silva, B., Giménez, A., Gutierrez-Yapu, D., Salamanca, E., Malheiros, A., 2013. Evaluation of antileishmanial activity of selected Brazilian plants and identification of the active principles. Evid. Based Complement. Alternat. Med., https://doi.org/10.1155/2013/265025.
Funari, C.S., De Almeida, L., Passalacqua, T.G., Martinez, I., Ambrosio, D.L., Cicarelli, R.M.B., Silva, D.H.S., Graminha, M.A.S., 2016. Oleanonic acid from Lippia lupulina (Verbenaceae) shows strong in vitro antileishmanial and antitrypanosomal ai]activity. Acta Amaz. 46, 411–416.
Gamboa-Leon, R., Vera-Ku, M., Peraza-Sanchez, S.R., Ku-Chulim, C., Horta-Baas, A., Rosado-Vallado, M., 2014. Antileishmanial activity of a mixture of Tridax procumbens and Allium sativum in mice. Parasite, https://doi.org/10.1051/parasite/2014016.
González-Coloma, A., Reina, M., Sáenz, C., Lacret, R., Ruiz-Mesia, L., Arán, V.J., Sanz, J., Martínez-Díaz, R.A., 2012. Antileishmanial, antitrypanosomal, and cytotoxic screening of ethnopharmacologically selected Peruvian plants. Parasitol. Res. 110, 1381–1392.
Guimaraes, L.R., Rodrigues, A.P., Marinho, P.S., Muller, A.H., Guilhon, G.M., Santos, L.S., do Nascimento, J.L., Silva, E.O., 2010. Activity of the julocrotine, a glutarimide alkaloid from Croton pullei var. glabrior, on Leishmania (L.) amazonensis. Parasitol. Res. 107, 1075–1081.
Hall, C.A., Hobby, T., Cipollini, M., 2006. Efficacy and mechanisms of alpha-solasonine-and alpha-solamargine-induced cytolysis on two strains of Trypanosoma cruzi. J. Chem. Ecol. 32, 2405–2416.
Hubert, D.J., Céline, N., Michel, N., Gogulamudi, V.R., Florence, N.T., Johnson, B.N., Bonaventure, N.T., Singh, I.P., Sehgal, R., 2013. In vitro leishmanicidal activity of some Cameroonian medicinal plants. Exp. Parasitol. 134, 304–308.
Iqbal, H., Khattak, B., Ayaz, S., Rehman, A., Ishfaq, M., Naseer Abbas, M., Rehman, H.U., Waheed, S., Wahab, A., 2012. Comparative efficacy of Aloe vera and Tamarix aphylla against cutaneous leishmaniasis. Int. J. Basic Med. Sci. Pharm. 2, 42–45.
Lindoso, J.A.L., Cunha, M.A., Queiroz, I.T., Moreira, C.H.V., 2016. Leishmaniasis-HIV coinfection: current challenges. HIV AIDS (Auckl.) 8, 147–156.
Lorenzi, H., 2000. Plantas Daninhas do Brasil: Terrestres, Aquáticas, Parasitas, e Tóxicas. Plantarum, Nova Odessa.
Machado, M., Dinis, A.M., Santos-Rosa, M., Alves, V., Salgueiro, L., Cavaleiro, C., Sousa, M.C., 2014. Activity of Thymus capitellatus volatile extract, 1.8-cineole and borneol against Leishmania species. Vet. Parasitol. 200, 39–49.
Mansour, R., Haouas, N., Kahla-Nakbi, A.B., Hammami, S., Mighri, Z., Mhenni, F., Babbab, H., 2013. The effect of Vitis vinifera L. leaves extract on Leishmania infantum. Iran J. Pharm. Res. 12, 349–355.
Martins, G.Z., Ph.D. Thesis 2013. Estudo Farmacognóstico e Screening Biológico de Solanum lycocarpum St. Hill (Solanaceae). Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, pp. 173.
Martins, G.Z., Moreira, R.R., Planeta, C.S., Almeida, A.E., Bastos, J.K., Salgueiro, L., Cavaleiro, C., Sousa, M.C., 2015. Effects of the extract and glycoalkaloids of Solanum lycocarpum St. Hill on Giardia lamblia trophozoites. Pharmacogn. Mag. 11, S161–S165.
Miranda, M.A., Ph.D. Thesis 2010. Avaliação do Potencial Antiparasitário do Extrato Alcaloídico de Alcalóides Esteroidais dos Frutos de Solanum lycocarpum A. St. -Hil. Faculdadede Ciências Farmacêuticas, Universidade de São Paulo, pp. 97.
Miranda, M.A., Magalhães, L.G., Tiossi, R.F., Kuehn, C.C., Oliveira, L.G., Rodrigues, V., McChesney, J.D., Bastos, J.K., 2012. Evaluation of the schistosomicidal activity of the steroidal alkaloids from Solanum lycocarpum fruits. Parasitol. Res. 111, 257–262.
Miranda, M.A., Tiossi, R.F., da Silva, M.R., Rodrigues, K.C., Kuehn, C.C., Rodrigues Oliveira, L.G., Albuquerque, S., McChesney, J.D., Lezama-Davila, C.M., Isaac-Marquez, A.P., Kenupp Bastos, J., 2013. In vitro Leishmanicidal and cytotoxic activities of the glycoalkaloids from Solanum lycocarpum (Solanaceae) fruits. Chem. Biodivers. 10, 642–648.
Mishra, B.B., Singh, R.K., Srivastava, A., Tripathi, V.J., Tiwari, V.K., 2009. Fighting against leishmaniasis: search of alkaloids as future true potential anti-Leishmanial agents. Mini. Rev. Med. Chem. 9, 107–123.
Moreira, R.R.D., Martins, G.Z., Magalhães, N.O., Almeida, A.E., Pietro, R.C.L.R., Silva, A.J.F., Cicarelli, R.M.B., 2013. In vitro trypanocidal activity of solamargine and extracts from Solanum palinacanthum and Solanum lycocarpum of Brazilian Cerrado. An. Acad. Bras. Ciênc. 85, 903–907.
Mothana, R.A., Al-Musayeib, N.M., Al-Ajmi, M.F., Cos, P., Maes, L., 2014. Evaluation of the in vitro antiplasmodial, antileishmanial, and antitrypanosomal activity of medicinal plants used in Saudi and Yemeni traditional medicine. Evid. Based Complement. Alternat. Med., https://doi.org/10.1155/2014/905639.
Munoz, V., Moretii, C., Sauvain, M., Caron, C., Porzel, A., Massiot, G., Richard, B., Men-Olivier, L.L., 1994. Isolation of bis-indole alkaloids with antileishmanial and antibacterial activities from Peschiera van heurkii (syn. Tabernaemontana van heurkii). Planta Med. 60, 455–459.
Murray, H.W., Berman, J.D., Davies, C.R., Saravia, N.G., 2005. Advances in leishmaniasis. Lancet 366, 1561–1577.
Natera, S., Machuca, C., Padrón-Nieves, M., Romero, A., Díaz, E., Ponte-Sucre, A., 2007. Leishmaniaspp.: proficiency of drug-resistant parasites. Int.J. Antimicrob. Agents 29, 637–642.
Ndjakou Lenta, B., Vonthron-Sénécheau, C., Fongang Soh, R., Tantangmo, F., Ngouela, S., Kaiser, M., Tsamo, E., Anton, R., Weniger, B., 2007. In vitro antiprotozoal activities and cytotoxicity of some selected Cameroonian medicinal plants. J. Ethnopharmacol. 111, 8–12.
Ogeto, T.K., Odhiambo, R.A., Shivairo, R.S., Muleke, C.I., Osero, B.O., Anjili, C., Ingonga, J.M., Osuga, I.M., 2013. Antileishmanial activity of Aloe secundiflora plant extracts against Leishmania major. Adv. Life. Sci. Technol. 13, 9–18.
Onocha, P.A., Ali, M.S., 2010. Antileishmaniasis, phytotoxicity and cytotoxicity of Nigerian Euphorbiaceous plants 2: Phyllanthus amarus and Phyllanthus muelle-rianus extracts. Afr. Sci. 11, 79–83.
Pham, T.T., Loiseau, P.M., Barratt, G., 2013. Strategies for the design of orally bioavailable antileishmanial treatments. Int. J. Pharm. 454, 539–552.
Rondon, F.C.M., Bevilaqua, C.M.L., Accioly, M.P., de Morais, S.M., de Andrade-Júnior, H.F., de Carvalho, C.A., Lima, J.C., Magalhães, H.C.R., 2012. In vitro efficacy of Coriandrum sativum, Lippia sidoides and Copaifera reticulata against Leishmania chagasi. Rev. Bras. Parasitol. Vet. 21, 185–191.
Sachdeva, H., Sehgal, R., Kaur, S., 2014a. Tinospora cordifolia as a protective and immunomodulatory agent in combination with cisplatin against murine visceral leishmaniasis. Exp. Parasitol. 137, 53–65.
Sachdeva, H., Sehgal, R., Kaur, S., 2014b. Asparagus racemosus ameliorates cisplatin induced toxicities and augments its antileishmanial activity by immunomodulation in vivo. Parasitol. Int. 63, 21–30.
Santos, V.A., Regasini, L.O., Nogueira, C.R., Passerini, G.D., Martinez, I., Bolzani, V.S., Graminha, M.A., Cicarelli, R.M., Furlan, M., 2012. Antiprotozoal sesquiterpene pyridine alkaloids from Maytenus ilicifolia. J. Nat. Prod. 75, 991–995.
Souza-Silva, F., Bourguignon, S.C., Pereira, B.A., Côrtes, L.M., de Oliveira, L.F., Henriques-Pons, A., Finkelstein, L.C., Ferreira, V.F., Carneiro, P.F., de Pinho, R.T., Caffarena, E.R., Alves, C.R., 2015. Epoxy-a-lapachone has in vitro and in vivo anti-Leishmania (Leishmania) amazonensis effects and inhibits eerine proteinase activity in this parasite. Antimicrob. Agents Chemother. 59, 1910–1918.
Tiossi, R.F.J., Miranda, M.A., de Sousa, J.P.B., Praça, F.S.G., Bentley, M.V.L.B., McChesney, J.D., Bastos, J.K., 2012. A validated reverse phase HPLC analytical method for quantitation of glycoalkaloids in Solanum lycocarpum and its extracts. J. Anal. Meth. Chem., https://doi.org/10.1155/2012/947836.
Torres, F.A.E., Passalacqua, T.G., Velásquez, A.M.A., Souza, R.A., Colepicolo Neto, P., Graminha, M.A.S., 2014. New drugs with antiprotozoal activity from marine algae: a review. Rev. Bras. Farmacogn. 24, 265–276.
Udalova, Z.V., Zinov’eva, S.V., Vasil’eva, I.S., Paseshnichenko, V.A., 2004. Correlation between the structure of plant steroids and their effects on phytoparasitic nematodes. Appl. Biochem. Microbiol. 40, 93–97.
Velásquez, A.M.A., de Souza, R.A., Passalacqua, T.G., Ribeiro, A.R., Scontri, M., Chin, C.M., de Almeida, L., Del Cistia, M.L., da Rosa, J.A., Mauro, A.E., Graminha, M.A.S., 2016. Antiprotozoal activity of the cyclopalladated complexes against Leishmania amazonensis and Trypanosoma cruzi. J. Braz. Chem. Soc. 27, 1032–1039.
Velásquez, A.M.A., Ribeiro, W.C., Venn, V., Castelli, S., Camargo, M.S., de Assis, R.P., de Souza, R.A., Ribeiro, A.R., Passalacqua, T.G., da Rosa, J.A., Baviera, A.M., Mauro, A.E., Desideri, A., Almeida-Amaral, E.E., Graminha, M.A.S., 2017. Efficacy of a binuclearcyclopalladated compound therapy for cutaneous leishmaniasis in the murine model of infection with Leishmania amazonensis and its inhibitory effect on topoisomerase 1B. Antimicrob. Agents Chemother. 61, e00688–e717.
Vieira Jr., G., Ferreira, P.M., Matos, L.G., Ferreira, E.C., Rodovalho, W., Ferri, P.H., Ferreira, H.D., Costa, E.A., 2003. Anti-inflammatory effect of Solanum lycocarpum fruits. Phytother. Res. 17, 892–896.
Waechter, A.I., Cavé, A., Hocquemiller, R., Bories, C., Mun˜oz, V., Fournet, A., 1999. Antiprotozoal activity of aporphine alkaloids isolated from Unonopsis buchtienii (Annonaceae). Phytother. Res. 13, 175–177.
WHO, 2018. Leishmaniasis. World Health Organization, http://www.who.int/leishmaniasis/en/ (accessed 21.03. 2018).
Yamamoto, E.S., Campos, B.L., Laurenti, M.D., Lago, J.H., Grecco Sdos, S., Corbett, C.E., Passero, L.F., 2014. Treatment with triterpenic fraction purified from Baccha-ris uncinella leaves inhibits Leishmania (Leishmania) amazonensis spreading and improves Th1 immune response in infected mice. Parasitol. Res. 113, 333–339.
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RRDM analyzed the data and drafted the paper. GZM contributed in collecting plant sample and identification, confection of herbarium. MASG designed the study, critically read the manuscript and wrote the manuscript. AMAV critically read the manuscript and wrote the manuscript. LS, MCS and CC critically read the manuscript. LCC, TGP and LA performed the biological assays. All the authors have read the final manuscript and approved the submission.
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da Clementino, L.C., Velásquez, A.M.A., Passalacqua, T.G. et al. In vitro activities of glycoalkaloids from the Solanum lycocarpum against Leishmania infantum. Rev. Bras. Farmacogn. 28, 673–677 (2018). https://doi.org/10.1016/j.bjp.2018.07.008
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DOI: https://doi.org/10.1016/j.bjp.2018.07.008