Antifungal effect of α-pinene alone and in association with antifungals against Candida albicans strains

Authors

DOI:

https://doi.org/10.33448/rsd-v11i4.27748

Keywords:

Candida; Terpene; Therapy; Natural product; Association.

Abstract

Caused by fungi of the genus Candida spp., candidiasis is reported as a public health problem, causing superficial and systemic infections. The increase in isolated resistant strains and the high toxicity of conventional antifungal agents have stimulated the search for alternatives to this scenario, such as bioproducts or isolated compounds, such as terpenes. Thus, it is important to investigate the antifungal activity of α-pinene alone and in association with antifungals against strains of Candida albicans. For this, the Minimum Inhibitory Concentration (MIC) and the Minimum Fungicide Concentration (MFC) were determined by the technique of microdilution in broth of the isolated terpene and the association assay (checkerboard) between α-pinene and antifungals, such as fluconazole and amphotericin. B. The α-pinene had a MIC between 128 and 512 µg/mL and the CFM had the same MIC values ​​against the 8 strains tested. The other concentrations could not determine the CFM, due to the fungal growth being greater than or equal to MICx4 (test limit). In the association trial, the interaction between α-pinene and fluconazole was indifferent, whereas the combinations between α-pinene with amphotericin B and nystatin obtained synergistic effects. Thus, this study strengthens α-pinene as a promising antifungal agent, as it exhibited strong inhibitory activity against Candida albicans strains, with a fungicidal nature. Additionally, it may be used in association with polyene derivatives (amphotericin B or nystatin) as an alternative in the treatment of candidiasis. It should be noted that more studies need to be carried out on the mechanism of action and toxicity of this compound.

References

Bakkali, F., Averbeck, S., Averbeck, D., & Idaomar, M. (2008). Biological effects of essential oils - A review. Food and Chemical Toxicology, 46(2), 446–475. https://doi.org/10.1016/j.fct.2007.09.106

Balouiri, M., Sadiki, M., & Ibnsouda, S. K. (2016). Methods for in vitro evaluating antimicrobial activity: A review. Journal of Pharmaceutical Analysis, 6(2), 71–79. https://doi.org/10.1016/j.jpha.2015.11.005

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). https://doi.org/10.3390/jof3040057

Celedonio, N. R. (2008). Estudo do mecanismo de ação antinociceptivo e antiedematogênico do óleo essencial de Croton argyrophylloides e seus constituintes: alfa-pineno e trans-cariofileno. Dissertação (Mestrado em Ciências Fisiológicas).

Cleeland, R. & Squires, E. (1991). Evaluation of new antimicrobials in vitro and in experimental animal infections. Antibiotics in laboratory medicine, 3, 739- 787.

CLSI. (2008). M27-A3 Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard-Third Edition. www.clsi.org.

Doi, A. M., Carlos, A., Pignatari, C., Edmond, M. B., Marra, R., Fernando, L., Camargo, A., & Siqueira, R. A. (2016). Epidemiology and Microbiologic Characterization of Nosocomial Candidemia from a Brazilian National Surveillance Program. 1–9. https://doi.org/10.1371/journal.pone.0146909

Dos Santos, A. O., Ueda-Nakamura, T., Dias Filho, B. P., Veiga, V. F., Pinto, A. C., & Nakamura, C. V. (2008). Antimicrobial activity of Brazilian copaiba oils obtained from different species of the Copaifera genus. Memorias Do Instituto Oswaldo Cruz, 103(3), 277–281. https://doi.org/10.1590/s0074-02762008005000015

Escalante, A., Gattuso, M., Pérez, P., & Zacchino, S. (2008). Evidence for the mechanism of action of the antifungal phytolaccoside B isolated from Phytolacca tetramera Hauman. Journal of Natural Products, 71(10), 1720–1725. https://doi.org/10.1021/np070660i

Eliopoulos, G. M. & Moellering, R. C. (1991). Antimicrobial combinations. Antibiotics in laboratory medicine, 434- 441.

Fortes, J. C. & Guedes, M. I. F. (2006). Atividade antimicrobiana do óleo essencial de Croton argyrophylloides muell arg e de frações isoladas dos extratos de Astronium urundeuva (Allemão) Engl. Anual da Sociedade Brasileira para o Progresso da Ciência, 58.

Frost, D. J., Brandt, K. D., Cugier, D., & Goldman, R. (1995). A Whole-Cell Candida albicans Assay for the Detection of Inhibitors towards Fungal Cell Wall Synthesis and Assembly. The Journal of Antibiotics, 48(4), 306–310. https://doi.org/10.7164/antibiotics.48.306

Hadacek, F., & Greger, H. (2000). Testing of antifungal natural products: Methodologies, comparability of results and assay choice. Phytochemical Analysis, 11(3), 137–147. https://doi.org/10.1002/(SICI)1099-1565(200005/06)11:3<137::AID-PCA514>3.0.CO;2-I

Holetz, F. B., Pessini, G. L., Sanches, N. R., Cortez, A. G., Nakamura, C. V., Prado, B., & Filho, D. (2002). Screening Pl Medicinais 2.Pdf. Mem Inst Oswaldo Cruz, 97(7), 1027–1031.

Jawale, C. V, & Biswas, P. S. (2021). ScienceDirect Local antifungal immunity in the kidney in disseminated candidiasis. Current Opinion in Microbiology, 62, 1–7. https://doi.org/10.1016/j.mib.2021.04.005

Jenks, J. D., Gangneux, J. P., Schwartz, I. S., Alastruey-Izquierdo, A., Lagrou, K., Thompson, G. R., Lass-Flörl, C., Hoenigl, M., Adamski, Z., Arikan Akdagli, S., Arsic-Arsenijevic, V., Cornely, O. A., Friberg, N., Gow, N., Hadina, S., Hamal, P., Juerna-Ellam, M., Klimko, N., Klingspor, L., … Verweij, P. (2020). Diagnosis of breakthrough fungal infections in the clinical mycology laboratory: An ecmm consensus statement. Journal of Fungi, 6(4), 1–19. https://doi.org/10.3390/jof6040216

Kathiravan, M. K., Salake, A. B., Chothe, A. S., Dudhe, P. B., Watode, R. P., Mukta, M. S., & Gadhwe, S. (2012). Bioorganic & Medicinal Chemistry The biology and chemistry of antifungal agents : A review. Bioorganic & Medicinal Chemistry, 20(19), 5678–5698. https://doi.org/10.1016/j.bmc.2012.04.045

Lass-Flörl, C., Samardzic, E., & Knoll, M. (2021). Serology anno 2021—fungal infections: from invasive to chronic. Clinical Microbiology and Infection, 27(9), 1230–1241. https://doi.org/10.1016/j.cmi.2021.02.005

Lima, I. O., Oliveira, R. D. A. G., Lima, E. D. O., De Souza, E. L., Farias, N. P., & Navarro, D. D. F. (2005). Inhibitory effect of some phytochemicals in the growth of yeasts potentially causing opportunistic infections. Revista Brasileira de Ciencias Farmaceuticas/Brazilian Journal of Pharmaceutical Sciences, 41(2), 199–203. https://doi.org/10.1590/S1516-93322005000200007

Machado, K. E., Cechinel Filho, V., Tessarolo, M. L., Mallmann, R., Meyre-Silva, C., & Bella Cruz, A. (2005). Potent antibacterial activity of Eugenia umbelliflora. Pharmaceutical Biology, 43(7), 636–639. https://doi.org/10.1080/13880200500303817

Ncube, N. S., Afolayan, A. J., & Okoh, A. I. (2008). Assessment techniques of antimicrobial properties of natural compounds of plant origin: Current methods and future trends. African Journal of Biotechnology, 7(12), 1797–1806. https://doi.org/10.5897/AJB07.613

Ninkuu, V., Zhang, L., Yan, J., Fu, Z., Yang, T., & Zeng, H. (2021). Biochemistry of terpenes and recent advances in plant protection. International Journal of Molecular Sciences, 22(11). https://doi.org/10.3390/ijms22115710

Oliveira, J. S.; Machado, K. C.; Freitas, R. M. (2014). Natural Products Applied a Neglected Diseases: Technological Forecasting. Revista Geintec: Gestação, Inovação e Tecnologias, 4, 729- 734.

Ostrosky, E. A., Mizumoto, M. K., Lima, M. E. L., Kaneko, T. M., Nishikawa, S. O., & Freitas, B. R. (2008). Métodos para avaliação da atividade antimicrobiana e determinação da Concentração Mínima Inibitória (CMI) de plantas medicinais. Revista Brasileira de Farmacognosia, 18(2), 301–307. https://doi.org/10.1590/s0102-695x2008000200026

Patil, S. (2015). Clinical Appearance of Oral Candida Infection and Therapeutic Strategies. 6(December), 1–10. https://doi.org/10.3389/fmicb.2015.01391

Rajput, S. B., & Mohan Karuppayil, S. (2013). Small molecules inhibit growth, viability and ergosterol biosynthesis in Candida albicans. SpringerPlus, 2(1), 1–6. https://doi.org/10.1186/2193-1801-2-26

Santos, G. C. D. O., Vasconcelos, C. C., Lopes, A. J. O., Rocha, F. M. G., & Monteiro, C. D. A. (2018). Candida Infections and Therapeutic Strategies : Mechanisms of Action for Traditional and Alternative Agents. 9(July), 1–23. https://doi.org/10.3389/fmicb.2018.01351

Sartoratto, A., Machado, A. L. M., Delarmelina, C., Figueira, G. M., Duarte, M. C. T., & Rehder, V. L. G. (2004). Composition and antimicrobial activity of essential oils from aromatic plants used in Brazil. Brazilian Journal of Microbiology, 35(4), 275–280. https://doi.org/10.1590/S1517-83822004000300001

Silva, A. C. R. da, Lopes, P. M., Azevedo, M. M. B. de, Costa, D. C. M., Alviano, C. S., & Alviano, D. S. (2012). Biological Activities of a-Pinene and β-Pinene Enantiomers. Molecules, 17(6), 6305–6316. https://doi.org/10.3390/molecules17066305

Song, B. (2020). A 5-Year Review of Invasive Fungal Infection at an Academic Medical. 10(October), 1–10. https://doi.org/10.3389/fcimb.2020.553648

Tacconi, L. (2018). Scientific Methodology. In Biodiversity and Ecological Economics. https://doi.org/10.4324/9781315096308-2

Valgus, J. M. (2003). What’s new in antifungals? Current Infectious Disease Reports, 5(1), 16–21. https://doi.org/10.1007/s11908-003-0060-4

Vieira, A. J. H. & Santos, J. I. (2017). Mecanismos de resistência de Candida albicans aos antifúngicos anfotericina B, fluconazol e caspofungina. RBAC, 49(3), 235- 239.

Zacchino, S. (2001). Estratégias para descoberta de novos agentes antifúngicos. Plantas medicinais sob a ótica da química medicinal moderna. Ed. Argos.

Published

27/03/2022

How to Cite

BARROS, D. B. de .; LIMA, L. de O. e .; SILVA, L. A. .; FONSECA , M. C. .; DINIZ-NETO, H.; ROCHA, W. P. da S. .; BELTRÃO, G. V. de M. .; CASTELLANO, L. R. C. .; GUERRA, F. Q. S. .; SILVA, M. V. da . Antifungal effect of α-pinene alone and in association with antifungals against Candida albicans strains. Research, Society and Development, [S. l.], v. 11, n. 4, p. e58711427748, 2022. DOI: 10.33448/rsd-v11i4.27748. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/27748. Acesso em: 26 apr. 2024.

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Section

Health Sciences