Anti-Candida albicans activity, cytotoxicity and interaction with antifungal drugs of essential oils and extracts from aromatic and medicinal plants

Información del artículo

Abstract

Objective

To determine anti-Candida albicans activity, cytotoxicity and drug interaction of essential oils and extracts from plants collected in Colombia.

Materials and methods

The antifungal activity was evaluated following the AFST-EUCAST protocol. With most active samples, the inhibition of the formation of germ tubes and budding, the in vitro pharmacodynamics, using time-kill assays, and the interaction with itraconazole and amphotericin B following the chequerboard technique were evaluated. The cytotoxicity assay for all samples was done using MTT.

Results

Strong activity in 17.57% of the samples was found. The lowest MIC values were obtained with Piper bredemeyeri Jacq and Lippia origanoides Kunth (B) oils and Morinda royoc L extract. The three samples inhibited the formation of germ tubes and budding. P. bredemeyeri Jacq oil and M. royoc L extract samples showed fungicidal activity at 2xMIC. A synergistic effect was obtained with the combination of P. bredemeyeri Jacq oil and itraconazole, but not for the combination with amphotericin B. Active samples against C. albicans were not cytotoxic on Vero cells ATCC CCL-81, excluding P. bredemeyeri Jacq oil.

Conclusions

The results of this study suggest that Colombian medicinal and aromatic plants represent an untapped source of compounds with anti-C. albicans activity that could be a resource in the development of new therapeutic natural products.

Key words:

Essential oils

extracts

Candida albicans

antifungal activity

cytotoxicity

synergism

Resumen

Objetivo

Determinar la actividad anti-Candida albicans, la citotoxicidad y la interacción con antifúngicos de aceites y extractos de plantas recolectadas en Colombia.

Materiales y métodos

La actividad antifúngica fue evaluada siguiendo el protocolo Antifungal Susceptibility Testing Subcommittee of the European Committee on Antimicrobial Susceptibility Testing (AFST-EUCAST). Con las muestras más activas se evaluó la inhibición de la formación de tubo germinal y la gemación, la farmacodinamia mediante curvas de tiempo muerte y la interacción con itraconazol y anfotericina B. Se determinó la citotoxicidad mediante la técnica MTT.

Resultados

Se encontró actividad en 17,57% de las muestras. La mayor actividad se obtuvo con los aceites de Piper bredemeyeri Jacq y Lippia origanoides Kunth (B) y el extracto de Morinda royoc L. Las tres muestras inhibieron la formación de tubo germinal y la gemación. El aceite de P. bredemeyeri Jacq y el extracto de M. royoc L mostraron actividad fungicida con dos veces la concentración inhibitoria mínima. Se encontró un efecto sinérgico por la combinación del aceite de P. bredemeyeri Jacq e itraconazol, pero no con anfotericina B. Las muestras activas no fueron citotóxicas, excepto el aceite de P. bredemeyeri Jacq.

Conclusión

Los resultados de este estudio sugieren que las plantas de Colombia son una fuente no explorada de compuestos con actividad anti-C. albicans, útiles para el desarrollo de nuevos productos terapéuticos.

Palabras clave:

aceites esenciales

extractos

Candida albicans

actividad antifúngica

citotoxicidad

sinergismo

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References

[1.]

M. Rai, D. Mares.

Plant-derived antimycotics: current trends and future prospects.

New York, (2003),

[2.]

R. Fonnegra, S. Jiménez.

Plantas medicinales aprobadas en Colombia Medellín.

Editorial Universidad de Antioquia, (2007),

[3.]

N.B. Parahitiyawa, Y.H. Samaranayake, L.P. Samaranayake, J. Ye, P.W. Tsang, B.P. Cheung, et al.

Interspecies variation in Candida biofilm formation studied using the Calgary biofilm device.

APMIS, 114 (2006), pp. 298-306

http://dx.doi.org/10.1111/j.1600-0463.2006.apm_394.x | Medline

[4.]

J.A. Cortés, P. Reyes, C. Gómez, G. Buitrago, A.L. Leal.

Fungal bloodstream infections in tertiary care hospitals in Colombia.

Rev Iberoam Micol, 28 (2011), pp. 74-78

http://dx.doi.org/10.1016/j.riam.2010.12.002 | Medline

[5.]

A. Zuluaga, C. de Bedout, C.A. Restrepo, H.H. Parra, M.A. Arteaga, A. Restrepo, et al.

Susceptibility to fluconazole and voriconazole of Candida species isolated from intensive care units patients in Medellin Colombia (2001-2007).

Rev Iberoam Micol, 27 (2010), pp. 125-129

http://dx.doi.org/10.1016/j.riam.2010.04.001 | Medline

[6.]

N.A. Torres, C.A. Álvarez, M.A. Rondón.

Evaluación mediante tres técnicas de susceptibilidad a fluconazol en especies de Candida aisladas en pacientes con infecciones invasoras: Bogotá.

Colombia. Rev Chil Infectol, 26 (2009), pp. 135-143

[7.]

C.C. Lai, C.K. Tan, Y.T. Huang, P.L. Shao, P.R. Hsueh.

Current challenges in the management of invasive fungal infections.

J Infect Chemother, 14 (2008), pp. 77-85

http://dx.doi.org/10.1007/s10156-007-0595-7 | Medline

[8.]

C. Cavaleiro, E. Pinto, M.J. Gonçalves, L. Salgueiro.

Antifungal activity of Juniperus essential oils against dermatophyte.

Aspergillus and Candida strains. J Appl Microbiol, 100 (2006), pp. 1333-1338

[9.]

E.E. Stashenko, B.E. Jaramillo, J.R. Martínez.

Comparison of different extraction methods for the analysis of volatile secondary metabolites of Lippia alba (Mill.) N.E Brown, grown in Colombia, and evaluation of its in vitro antioxidant activity.

J Chromatogr A, 1025 (2004), pp. 93-103

Medline

[10.]

M. Cuenca-Estrella, C.B. Moore, F. Barchiesi, J. Bille, E. Chryssanthou, D.W. Denning, et al.

Multicenter evaluation of the reproducibility of the proposed antifungal susceptibility testing method for fermentative yeasts of the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antimicrobial Susceptibility Testing (AFST-EUCAST).

Clin Microbiol Infect, 9 (2003), pp. 467-474

Medline

[11.]

K. Ishida, J.C. de Mello, D.A. Cortez, B.P. Filho, T. Ueda-Nakamura, C.V. Nakamura.

Influence of tannins from Stryphnodendron adstringens on growth and virulence factors of Candida albicans.

J Antimicrob Chemother, 58 (2006), pp. 942-949

http://dx.doi.org/10.1093/jac/dkl377 | Medline

[12.]

M.E. Klepser, E.J. Ernst, R.E. Lewis, M.E. Ernst, M.A. Pfaller.

Influence of test conditions on antifungal time-kill curve results: Proposal for standardized methods.

Antimicrob Agents Chemother, 42 (1998), pp. 1207-1212

Medline

[13.]

R.G. Vitale, J. Afeltra, E. Dannaoui.

Antifungal combinations.

Humana Press, (2005),

[14.]

L.A. Betancur-Galvis, J.E. Forero, G.E. Morales, J.E. Forero, J. Roldán.

Cytotoxic and antiviral activities of Colombian medicinal plant extracts of the Euphorbia genus.

Mem Inst Oswaldo Cruz, 97 (2002), pp. 541-546

Medline

[15.]

M.R. Jacob, I.A. Walker.

Natural products and antifungal drug discovery.

Humana Press, (2005),

[16.]

N. Aligiannis, E. Kalpoutzakis, S. Mitaku, I.B. Chinou.

Composition and antimicrobial activity of the essential oils of two Origanum species.

J Agric Food Chem, 49 (2001), pp. 4168-4170

Medline

[17.]

M.C. Duarte, G.M. Figueira, A. Sartoratto, V.L. Rehder, C. Delarmelina.

Anti-Candida activity of Brazilian medicinal plants.

J Ethnopharmacol, 97 (2005), pp. 305-311

http://dx.doi.org/10.1016/j.jep.2004.11.016 | Medline

[18.]

F.B. Holetz, G.L. Pessini, N.R. Sanches, D.A. Cortez, C.V. Nakamura, B.P. Filho.

Screening of some plants used in the Brazilian folk medicine for the treatment of infectious diseases.

Mem Inst Oswaldo Cruz, 97 (2002), pp. 1027-1031

Medline

[19.]

A. López, J.B. Hudson, G.H. Towers.

Antiviral and antimicrobial activities of Colombian medicinal plants.

J Ethnopharmacol, 77 (2001), pp. 189-196

Medline

[20.]

D.R. Oliveira, G.G. Leitao, H.R. Bizzo, D. Lopes, D.S. Alviano, C.S. Alviano, et al.

Chemical and antimicrobial analyses of essential oil of Lippia origanoides H.B.K.

Food Chemistry, 101 (2007), pp. 236-240

[21.]

R.A. Calderone, Fonzi W.A..

Virulence factors of Candida albicans.

Trends Microbiol, 9 (2001), pp. 327-335

Medline

[22.]

K.A. Toenjes, S.M. Munsee, A.S. Ibrahim, R. Jeffrey, J.E. Edwards Jr., D.I. Johnson.

Small-molecule inhibitors of the budded-to-hyphal-form transition in the pathogenic yeast Candida albicans.

Antimicrob Agents Chemother, 49 (2005), pp. 963-972

http://dx.doi.org/10.1128/AAC.49.3.963-972.2005 | Medline

[23.]

S. Hawser, K. Islam.

Comparisons of the effects of fungicidal and fungistatic antifungal agents on the morphogenetic transformation of Candida albicans.

J Antimicrob Chemother, 43 (1999), pp. 411-413

Medline

[24.]

C.F. Carson, K.A. Hammer, T.V. Riley.

Melaleuca alternifolia (tea tree) oil: A review of antimicrobial and other medicinal properties.

Clin Microbiol Rev, 19 (2006), pp. 50-62

http://dx.doi.org/10.1128/CMR.19.1.50-62.2006 | Medline

[25.]

A. Jandourek, J.K. Vaishampayan, J.A. Vazquez.

Efficacy of Melaleuca oral solution for the treatment of fluconazole refractory oral candidiasis in AIDS. patients.

AIDS, 12 (1998), pp. 1033-1037

Medline

[26.]

K.A. Hammer, C.F. Carson, T.V. Riley.

In vitro activity of essential oils, in particular Melaleuca alternifolia (tea tree) oil and tea tree oil products, against Candida spp.

J Antimicrob Chemother, 42 (1998), pp. 591-595

Medline

[27.]

C.V. Nakamura, K. Ishida, L.C. Faccin, B.P. Filho, D.A. Cortez, S. Rozental, et al.

In vitro activity of essential oil from Ocimum gratissimum L. against four Candida species.

Res Microbiol, 155 (2004), pp. 579-586

http://dx.doi.org/10.1016/j.resmic.2004.04.004 | Medline

[28.]

M.A. Pfaller, D.J. Sheehan, J.H. Rex.

Determination of fungicidal activities against yeasts and molds: Lessons learned from bactericidal testing and the need for standardization.

Clin Microbiol Rev, 17 (2004), pp. 268-280

Medline

[29.]

B.C. Monk, A. Goffeau.

Outwitting multidrug resistance to antifungals.

Science, 321 (2008), pp. 367-369

http://dx.doi.org/10.1126/science.1159746 | Medline

[30.]

I.O. Lima, R.G. Oliveira, E.O. Lima, E.L. de Souza, N.P. Farias, D.F. Navarro.

Inhibitory effect of some phytochemicals in the growth of yeasts potentially causing opportunistic infections.

Braz J Pharm Sci, 41 (2005), pp. 199-203

[31.]

S.D. Cox, C.M. Mann, J.L. Markham, H.C. Bell, J.E. Gustafson, J.R. Warmington, et al.

The mode of antimicrobial action of the essential oil of Melaleuca alternifolia (tea tree oil).

J Appl Microbiol, 88 (2000), pp. 170-175

Medline

[32.]

W. Xiang, Q.S. Song, H.J. Zhang, S.P. Guo.

Antimicrobial anthraquinones from Morinda angustifolia.

Fitoterapia, 79 (2008), pp. 501-504

http://dx.doi.org/10.1016/j.fitote.2008.04.008 | Medline

[33.]

S. Shin, S. Lim.

Antifungal effects of herbal essential oils alone and in combination with ketoconazole against Trichophyton spp.

J Appl Microbiol, 97 (2004), pp. 1289-1296

http://dx.doi.org/10.1111/j.1365-2672.2004.02417.x | Medline

[34.]

M. Suffness, J.M. Pezzuto.

Assays related to cancer drug discovery.

Academic Press, (1990),

[35.]

Y. González, I. Scull, A.M. Bada, B. González, D. Fuentes, M.E. Arteaga, et al.

Ensayo de toxicidad a dosis repetidas del extracto acuoso de Morinda royoc L. en ratas Cenp: SPRD.

Rev Cubana Plant Med, vol 8 (2003),

[36.]

E. Chivian.

Biodiversity: Its importance to human health. A Project of the Center for Health and the Global Environment.

Cambidge: Harvard Medical School, (2002),

[37.]

M.E. Wall, M.C. Wani.

Camptothecin and taxol: From discovery to clinic.

J Ethnopharmacol, 51 (1996), pp. 239-254

Medline

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