Exploring antifungal potential: The flavonoid composition of Machaerium villosum extracts against Cryptococcus neoformans

Authors

DOI:

https://doi.org/10.33448/rsd-v13i1.44604

Keywords:

Jacarandá; Antifungal; Flavonol.

Abstract

The escalating prevalence of fungal infections, coupled with the limitations and adverse effects associated with existing antifungal drugs, necessitates the exploration of alternative therapeutic approaches. The objective of this study was, therefore, to conduct a chemical analysis and assess the biological potential of the hydroethanolic extract obtained from the leaves of Machaerium villosum. Thus, this study investigates the extract from this plant, which belongs to the Fabaceae family, known for its rich flavonoid content. Employing UHPLC-ESI-IT-MS/MS, the extract was characterized, revealing the presence of various flavonoids, including glycosylated derivatives of kaempferol and quercetin, along with organic acids and fatty acid derivatives. The total flavonoid content was quantified at 45.7 mg/g. Subsequent antifungal evaluation unveiled significant activity against Cryptococcus neoformans, with a minimum inhibitory concentration (MIC) of 16 μg/ml and fungicidal action at 256 μg/ml. The observed efficacy against C. neoformans aligns with the documented antifungal properties of flavonoids, which disrupt membrane integrity and impede crucial cellular processes. The findings suggest that M. villosum extract, particularly its flavonoid constituents, holds promise as a potential source for developing new antifungal therapies.

References

Aboody, M. S. A. & Mickymaray, S. (2020). Anti-Fungal Efficacy and Mechanisms of Flavonoids. Antibiotics (Basel), 9(2). https://doi.org/10.3390/antibiotics9020045

Almeida, C. de. & Viani, R. A. G. (2020). Espécies arbóreas plantadas na restauração da Mata Atlântica (versão 2). Laboratório de Silvicultura e Pesquisas Florestais, LASPEFUFSCar.

Andersen, O. M. & Markham, K. R. (2006). Flavonoids: chemistry, biochemistry, and applications. Taylor & Francis Group.

Beelders, T. (2011). HPLC method development for the characterisation of the flavonoid and phenolic acid composition of rooibos (Aspalathus linearis) infusions. [Dissertação de Mestrado, Universidade de Stellenbosch]. https://core.ac.uk/download/pdf/37344789.pdf

Bento, C. C., Ferreira, M. J. P., Proença, G. T. de., Tahira, L. S., Sartori, A. L. B. & Sannomiya, M. (2022). Análises por cromatografia líquida de alta eficiência acoplada a detector de ultravioleta de arranjo de diodos (CLAE-UV-DAD) de extratos de Machaerium acutifolium Vogel e o seu potencial antioxidante. In Agendas Locais e Globais da Sustentabilidade: Ciência, Tecnologia, Gestão e Sociedade. Blucher. https://doi.org/10.5151/9786555501551

Bermas, A. & Geddes-Mcalister, J. (2022). Combatting the evolution of antifungal resistance in Cryptococcus neoformans. Molecular Microbiology, 114(5), 721– 734. https://doi.org/10.1111/mmi.14565

Bongomin, F.; Gago, S., Oladele, R. O. & Denning, D. W. (2017). Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision. Journal of fungi, 3(4), 57. https://doi.org/10.3390/jof3040057

Brown, G. D., Denning, D. W.; Gow, N. A., Levitz, S. M.; Netea, M. G. & White, T. C. (2012). Hidden killers: human fungal infections. Science translational medicine, 4(165), 165rv13. https://doi.org/10.1126/scitranslmed.3004404

Buzgaia, N., Lee, S. Y., Rukayadi, Y., Abas, F., Shaari, K. (2021). Antioxidant Activity, α-Glucosidase Inhibition and UHPLC–ESI–MS/MS Profile of Shmar (Arbutus pavarii Pamp). Plants, 10(1659). https://doi.org/10.3390/plants10081659

Cádiz-Gurrea, M. D., Fernández-Arroyo, S., Joven, J. & Segura‐Carretero, A. (2013). Comprehensive characterization by UHPLC-ESI-Q-TOF-MS from an Eryngium bourgatii extract and their antioxidant and anti-inflammatory activities. Food Research International, 50, 197-204. https://doi.org/10.1016/j.foodres.2012.09.038

Carvalho, A. A.; Santos, L., Sousa, R. P. de., Freitas, J. S. de., Araújo, B. Q. & Chaves, M. H. (2019). Identificação de flavonoides das folhas de Machaerium acutifolium (Papilionoideae-fabaceae) por espectrometria de massas. In Ciências Biológicas Campo Promissor em Pesquisa. Atena. https://doi.org/10.22533/at.ed.82619131113

Chen, G., Li, X., Saleri, F. & Guo, M. (2016). Analysis of Flavonoids in Rhamnus davurica and Its Antiproliferative Activities. Molecules, 21(10), 1275. https://doi.org/10.3390/molecules21101275

Chintalapudi, K. & Badu-Tawiah, A. K. (2020). An integrated electrocatalytic nESI-MS platform for quantification of fatty acid isomers directly from untreated biofluids. Chemical science, 11(36), 9891–9897. https://doi.org/10.1039/d0sc03403g

CLSI. (2017). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi. (2017). (3a ed.), CLSI standard M27. Wayne, PA: Clinical and Laboratory Standards Institute.

CLSI. (2017). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. 4th ed. CLSI standard M27. Wayne, PA: Clinical and Laboratory Standards Institute.

Gouveia, S. & Castilho, P. C. (2011). Characterisation of phenolic acid derivatives and flavonoids from different morphological parts of Helichrysum obconicum by a RP-HPLC-DAD-(-)-ESI-MSn method. Food chemistry, 129(2), 333–344. https://doi.org/10.1016/j.foodchem.2011.04.078

Derengowski, L. da S. (2011). Caracterização da resposta de fungos patogênicos a diferentes condições de interação intra e interreinos. [Tese de Doutorado, Universidade de Brasília]. Repositório Institucional as UnB. https://repositorio.unb.br/handle/10482/9529?locale=pt_BR

Ding, S., Dudley, E., Plummer, S., Tang, J., Newton, R. P. & Brenton, A. G. (2008). Fingerprint profile of Ginkgo biloba nutritional supplements by LC/ESI-MS/MS. Phytochemistry, 69(7), 1555–1564. https://doi.org/10.1016/j.phytochem.2008.01.026

Djouossi, M. G., Tamokou, J. de D., Ngnokam, D., Kuiate, J. R., Tapondjou, L. A., Harakat, D. & Voutquenne-Nazabadioko, L. (2015). Antimicrobial and antioxidant flavonoids from the leaves of Oncoba spinosa Forssk. (Salicaceae). BMC Complement Altern Med, 15(134). https://doi.org/10.1186/s12906-015-0660-1

Fathoni, A., Saepudin, E., Cahyana, A. H., Rahayu, D. U. C. & Haib, J. (2017). Identification of nonvolatile compounds in clove (Syzygium aromaticum) from Manado. AIP Conference Proceedings, 10(1). https://doi.org/10.1063/1.4991183

Food and Drug Administration, HHS (2014). Establishing a list of qualifying pathogens under the Food and Drug Administration Safety and Innovation Act. Final rule. Federal register, 79(108), 32464–32481.

Fraternale, D., Ricci, D., Verardo, G., Gorassini, A., Stocchia, V. & Sestili, P. (2015). Activity of Vitis vinifera Tendrils Extract Against Phytopathogenic Fungi. Natural product communications, 10(6), 1037–1042. https://doi.org/10.1177/1934578X1501000661

Garcia, M. B., Venturin, C., Rodas, C. L., Carlos, L., Higashikawa, E. M. & Farias, E. de S. (2010). Avaliação do crescimento de mudas de Machaerium villosum Vogel cultivadas em solução nutritiva. XIX Congresso de Pós-graduação da UFLA, Minas Gerais. http://www.sbpcnet.org.br/livro/lavras/resumos/1967.pdf

Gilbert, B.; Souza, J. P. de., Fascio, M., Kitagawa, M., Nascimento, S. S. C., Fortes, C. C., Seabra, A. do Prado; Pellegrino, J. (1970). Schistosomiasis: Protection against infection by terpenoids. Anais da Academia Brasileira de Ciências, 42, 397-400.

Giudice-Neto, J., Ramos, R. F.; Moraes, E. M. de., Silva, M. J. da. & Solferini, V. N. (2014). Isolation and characterization of ten new microsatellite markers in Machaerium villosum Vogel (Fabaceae), Hoehnea, 41(1), 77-80. https://doi.org/10.1590/S2236-89062014000100007

Grati, W., Samet, S., Bouzayani, B., Ayachi, A., Treilhou, M., Téné, N. & Mezghani-Jarraya, R. (2022). HESI-MS/MS Analysis of Phenolic Compounds from Calendula aegyptiaca Fruits Extracts and Evaluation of Their Antioxidant Activities. Molecules, 27 (2314). https://doi.org/10.3390/molecules27072314

Higa, C. K., Pauletti, M. P., Gamboa, I. C., Silva, D. H. D., Torres, L. B., Furlan, M.; Young, M. C. M.; P. Lopes, N. P. & Bolzani, V. da S. (2006). Novo derivado fenólico de Machaerium villosum (Leguminosae – Papilionoideae). In: Livro de Resumos, 29a. Reunião Anual da Sociedade Brasileira de Química. http://sec.sbq.org.br/cdrom/29ra/resumos/T1189-1.pdf

Ivanov, M., Kannan, A., Stojković, D. S., Glamočlija, J., Calhelha, R. C., Ferreira, I. C. F. R., Sanglard, D. & Soković, M. (2020). Flavones, Flavonols, and Glycosylated Derivatives-Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity. Pharmaceuticals (Basel), 14(1), 27. https://doi.org/10.3390/ph14010027

Kumar, S., Singh, A. & Kumar, B. (2017). Identification and characterization of phenolics and terpenoids from ethanolic extracts of Phyllanthus species by HPLC-ESI-QTOF-MS/MS. Journal of pharmaceutical analysis, 7 (4), 214–222. https://doi.org/10.1016/j.jpha.2017.01.005

Li, Z. H., Guo, H., Xu, W. B., Ge, J., Li, X., Alimu, M. & He, D. J. (2016). Rapid Identification of Flavonoid Constituents Directly from PTP1B Inhibitive Extract of Raspberry (Rubus idaeus L.) Leaves by HPLC–ESI–QTOF–MS-MS. Journal of Chromatographic Science, 54(5), 805–810. https://doi.org/10.1093/chromsci/bmw016

Lima, N. M., Santos, V. N. C. & Laporta, F. A. (2018). Chemodiversity, bioactivity, and chemosystematics of the genus Inga (FABACEAE): A Brief Review. Revista Virtual de Química, 10(3), 459-473. https://doi.org/10.21577/1984-6835.20180035

Limper, A. H., Adenis, A., Le, T. & Harrison, T. S. (2017). Fungal infections in HIV/AIDS. The Lancet. Infectious diseases, 17(11), e334–e343. https://doi.org/10.1016/S1473-3099(17)30303-1

Liu, Y. & Seeram, N. P. (2018). Liquid chromatography coupled with time-of-flight tandem mass spectrometry for comprehensive phenolic characterization of pomegranate fruit and flower extracts used as ingredients in botanical dietary supplements. Journal of separation science, 41(15), 3022–3033. https://doi.org/10.1002/jssc.201800480

Lopes, J. A., Rodrigues, V. P., Tangerina, M. M. P., Rocha, L. R. M. D., Nishijima, C. M., Nunes, V. V. A.; Almeida, L. F. R.; Vilegas, W., Santos, A. R. S. D., Sannomiya, M., & Hiruma-Lima, C. A. (2020). Machaerium hirtum (Vell.) Stellfeld Alleviates Acute Pain and Inflammation: Potential Mechanisms of Action. Biomolecules, 10 (4), 590. https://doi.org/10.3390/biom10040590

Machado, O. V. O., Patrocínio, M. C. A., Medeiros, M. S., Bandeira, T. de J. P. G. (2019). Antimicrobianos: revisão geral para graduandos e generalistas. EdUnichristus.

Melo, V. V., Duarte, I. de P., Soares, A. Q. (2012). Guia de antimicrobianos. Universidade Federal de Goiás - Hospital das Clínicas.

Oliveira, V. M., Carraro, E., Auler, M. E. & Nour, K. (2016). Quercetin and rutin as potential agents antifungal against Cryptococcus spp. Brazilian journal of biology, 76 (4), 1029-1034. http://dx.doi.org/10.1590/1519-6984.07415

Parejo, I., Jauregui, O., Sánchez-Rabaneda, F., Viladomat, F., Bastida, J. & Codina, C. (2004) . Separation and Characterization of Phenolic Compounds in Fennel (Foeniculum vulgare) Using Liquid Chromatography−Negative Electrospray Ionization Tandem Mass Spectrometry. Journal of Agricultural and Food Chemistry (52) 12, 3679-3687. http://dx.doi.org/ 10.1021/jf030813h

Prista. L. N. (1995). Tecnologia framauceutica II. (5a ed.). Fundação Calouste Gulbenkian.

Qiu, Y., He, D., Yang, J., Lukai, M., Kaiqi, Z. & Yong, C. (2020). Kaempferol separated from Camellia oleifera meal by high-speed countercurrent chromatography for antibacterial application. Eur Food Res Technol, 246, 2383–2397, 2020. https://doi.org/10.1007/s00217-020-03582-0

Rajasingham, R., Smith, R. M., Park, B. J., Jarvis, J. N., Govender, N. P., Chiller, T. M., Denning, D. W., Loyse, A. & Boulware, D. R. (2017). Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. The Lancet. Infectious diseases, 17(8), 873–881. https://doi.org/10.1016/S1473-3099(17)30243-8

Roriz, C. L., Barros, L., Carvalho, A. M., Santos-Buelga, C. & Ferreira, I. C.F.R. (2014). Pterospartum tridentatum, Gomphrena globosa and Cymbopogon citratus: A phytochemical study focused on antioxidant compounds. Food Research International, 62, 684-693. https://doi.org/10.1016/j.foodres.2014.04.036

Sannomiya, M. Ruy, J. V. J., Tahira, L. S., Bento, C. C., Tangerina, M. M. P., Sartori, A. L. B., Bauab, T. M.; Hiruma-Lima, C. A., Vilegas, W. (2020). Química e avaliação das atividades antiinflamatória, antiúlcera e antimicrobiana: Machaerium eriocarpum Benth. Produção e Controle de Produtos Naturais 2, Editora Atena.

Santana, D. B., Costa, R. C. da, Araújo, R. M., Paula, J. E. de, Silveira, E. R., Braz-Filho, R. & Espindola, L. S. (2015). Activity of Fabaceae species extracts against fungi and Leishmania: vatacarpan as a novel potent anti-Candida agente. Revista Brasileira de Farmacognosia, 25(4), 401-406. https://doi.org/10.1016/j.bjp.2015.07.012

Santos, A. B. dos., Silva, D. H. S., Bolzani, V. da S., Santos, L. Á., Schidt, T. M. & Baffa, O. (2009). Antioxidant properties of plant extracts: an EPR and DFT comparative study of the reaction with DPPH, TEMPOL and spin trap DMPO. Journal of the Brazilian Chemical Society, 20(8), 1483-1492, 2009. https://doi.org/10.1590/S0103-50532009000800015

Santos Jr., I. D. dos., Souza, I. A. M., Borges, R. G., Souza, L. B. S. de; Santana, W. J. de. & Coutinho, H. D. M. (2005). Característica gerais da ação, do tratamento e da resistência fúngica ao fluconazol / General traits of action, treatment and fungal resistance to fluconazol, Scientia Medica, 15(3), 189-197. Recuperado de https://revistaseletronicas.pucrs.br/ojs/index.php/scientiamedica/article/view/1566

Santos, P. M. L., Schripsema, J., Kuster, R. M. (2005). Flavonóides O-glicosilados de Croton campestris St. Hill. (Euphorbiaceae). Revista Brasileira de Farmacognosia, 15(4), 321-325. https://doi.org/10.1590/S0102-695X2005000400011

Silva, M. J. D., Simonet, A. M., Silva, N. C., Dias, A. L. T.; Vilegas, W. & Macías, F. A. (2019). Bioassay-Guided Isolation of Fungistatic Compounds from Mimosa caesalpiniifolia Leaves. Journal of natural products, 82(6), 1496–1502. https://doi.org/10.1021/acs.jnatprod.8b01025

Simirgiotis, M. J., Benites, J., Areche, C. & Sepúlveda, B. (2015). Antioxidant capacities and analysis of phenolic compounds in three endemic Nolana species by HPLC-PDA-ESI-MS. Molecules, 20(6), 11490-11507. https://doi.org/10.3390/molecules200611490

Tahira, L. S. (2022). Estudo químico e fitotóxico do extrato hidroetanólico das folhas de Machaerium amplum Benth. [Dissertação de Mestrado em Ciências, Escola de Artes, Ciências e Humanidades - Universidade de São Paulo]. Bibliotoca Digital de Teses e Dissertações da USP. https://www.teses.usp.br/teses/disponiveis/100/100136/tde-28012022-093234/publico/LucianaSayuriTahira_versaocorrigida.pdf

Tahira, L. S., Tino, R. A., Bento, C. C., Tangerina, M. M. P., de Almeida, L. F. R., Franco, D. M., sartori, A. L. B. & Sannomiya, M. (2021). The lupeol content in Machaerium species by HPLC-APCI-MS/MS and the allelopathic action. Journal of Horticulture and Forestry, 13(2), 44-50. https://doi.org/10.5897/JHF2021.0668

Tahira, L. S., Torres, P., Ferreira, M. J. P., Tangerina, M. M. P., Santos-Lima, D., Kamikawachi, R. C., Vilegas, W., Sartori, A. L. B. & Sannomiya, M. (2022). Phytotoxic action of Machaerium amplum Benth. leaves extract. International Journal of Agriculture and Envrinmental Research, 8(1), 46-62. https://doi.org/10.22004/ag.econ.333818

Tannus, M. M. (2017). Poluição ambiental causada por fármacos para usos humanos e veterinários. Revista Acadêmica Oswaldo Cruz, 15. http://revista.oswaldocruz.br/Edicao_15/Artigos

Tatsimo, S. J. N., Tamokou, J. D. D., Havyarimana, L., Dezső, C., Peter, F., Judit, H., Jules-Roger, K. & Pierre, T. (2012). Antimicrobial and antioxidant activity of kaempferol rhamnoside derivatives from Bryophyllum pinnatum. BMC Res Notes, 5(158). https://doi.org/10.1186/1756-0500-5-158

Tavares, W. (2014). Antibióticos e quimioterápicos para o clínico (3a ed.) Atheneu.

Taylor, V. F., March, R. E., Longerich, H. P. & Stadey, C. J. (2005). A mass spectrometric study of glucose, sucrose, and fructose using an inductively coupled plasma and electrospray ionization. International Journal of Mass Spectrometry, 243(1), 71-84. https://doi.org/10.1016/j.ijms.2005.01.001.

Vihakas, M. (2014). Flavonoids and other phenolic compounds: characterization and interactions with lepidopteran and sawfly larvae. [Tese de Doutorado, University of Turku]. Department of Chemistry/Faculty of Mathematics and Natural Sciences.

Yhiya, M. A., Amani M. M., Mona G. Z. & Mohamed S. A. (2015). The genus Machaerium (Fabaceae): taxonomy, phytochemistry, traditional uses and biological activities, Natural Product Research: Formerly Natural Product Letters, 29(15), 1388-1405. http://dx.doi.org/10.1080/14786419.2014.1003062

Zhang, Y., Xiong, H., Xu, X., Xue, X., Liu, M., Xu, S., Liu, H., Gao, Y., Zhang, H. & Li, X. (2018). Compounds Identification in Semen Cuscutae by Ultra-High-Performance Liquid Chromatography (UPLCs) Coupled to Electrospray Ionization Mass Spectrometry. Molecules, 23(5), 1199. https://doi.org/10.3390/molecules23051199

Downloads

Published

03/01/2024

How to Cite

DOURADO, C. P.; KAMIKAWACHI, R. C.; FERREIRA, M. J. P. .; SARTORI, Ângela L. B.; RODRIGUES, C. M.; SPADARI, C. de C.; ISHIDA, K.; SANNOMIYA, M. . Exploring antifungal potential: The flavonoid composition of Machaerium villosum extracts against Cryptococcus neoformans. Research, Society and Development, [S. l.], v. 13, n. 1, p. e1613144604, 2024. DOI: 10.33448/rsd-v13i1.44604. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/44604. Acesso em: 12 jun. 2024.

Issue

Section

Exact and Earth Sciences