Antifungal Activity of Traditional Medicinal Plants from Argentina: Effect of their Combination with Antifungal Drugs

Page: [75 - 95] Pages: 21

  • * (Excluding Mailing and Handling)

Abstract

Background and Objective: The incidence of fungal infections has experienced a marked increase in the last two decades being limited to a few drugs with serious drawbacks. Combination therapy has emerged as an approach to improve the efficacy of currently used antifungal therapy that also may delay the evolution of resistance.

Method: The objectives of this work are to present a bibliographic search on the plants used in traditional medicine in Argentina for ailments related to fungal infections and to investigate the antifungal activity of currently used antifungal drugs in combination with natural extracts.

Results: Results of the bibliographic investigation showed that 153 species belonging to 56 families and 120 genera from Argentina are applied to treat signs and symptoms considered to maintain ethnopharmacological uses related to fungal infections, mainly for skin and mucosal conditions.

Conclusion: Regarding the evaluation of the antifungal activity of combinations between extracts and antifungal drugs, we observed that extracts from plants species belonging to a genera traditionally used for ailments related to fungal infections have more chances of enhancing the activity of amphotericin B, fluconazole and itraconazole. In addition, we observed that there is a greater chance of finding an enhancement in the activity of the commercial antifungals when the combination is performed with extracts that have shown activity in solitary. Nevertheless, inactive extracts that would have been discarded according to the classic strategy displayed activity in combination and they continue being potential candidates in the search for new antifungals.

Keywords: Antifungal, Argentinean plants, Candida albicans, combination, enhancers, ethnopharmacology.

Graphical Abstract

[1]
Roemer T, Krysan DJ. Antifungal drug development: challenges, unmet clinical needs, and new approaches. Cold Spring Harb Perspect Med 2014; 4: a019703.
[2]
Tuite NL, Lacey K. Overview of invasive fungal infections.In: O'Connor L, Glynn B, Eds Fungal Diagnostics: Methods and Protocols. New Jersey: Humana Press 2013; pp. 1-23.
[3]
Ameen M. Epidemiology of superficial fungal infections. Clin Dermatol 2010; 28: 197-201.
[4]
Odds FC, Brown AJ, Gow NA. Antifungal agents: Mechanisms of action. Trends Microbiol 2003; 11: 272-9.
[5]
Akins RA, Sobel JD. Antifungal targets, mechanisms of action, and resistance in Candida albicans. In :Mayers DL, Sobel JD, Ouellette M, Kaye KS, Marchaim D, Eds Antimicrobial drug resistance. New York: Springer Cham 2017; pp. 429-75.
[6]
Spitzer M, Robbins N, Wright GD. Combinatorial strategies for combating invasive fungal infections. Virulence 2017; 8: 169-85.
[7]
Svetaz LA, Postigo A, Butassi E, et al. Antifungal drugs combinations: a patent review 2000-2015. Expert Opin Ther Pat 2016; 26: 439-53.
[8]
Baym M, Stone LK, Kishony R. Multidrug evolutionary strategies to reverse antibiotic resistance. Science 2016; 351: aad3292.
[9]
Koehn F, Carter G. The evolving role of natural products in drug discovery. ‎. Nat Rev Drug Discov 2005; 4: 206-20.
[10]
Nisbet LJ, Moore M. Will natural products remain an important source of drug research for the future? Curr Opin Biotechnol 1997; 8: 708-12.
[11]
Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 2016; 79: 629-61.
[12]
Ostrosky-Zeichner L, Casadevall A, Galgiani JN, et al. An insight into the antifungal pipeline: Selected new molecules and beyond. Nat Rev Drug Discov 2010; 9: 719-27.
[13]
World Health Organization. Estrategia de la OMS sobre medicina tradicional 2002-2005. Ginebra: Organización Mundial de la Salud 2002.
[14]
Canton M, Onofre SB. Interference from extracts of Baccharis dracunculifolia DC., Asteraceae, on the activity of antibiotics used in the clinic. Rev Bras Farmacogn 2010; 20: 348-54.
[15]
Maia CN, da Silva CAM, Junior RR, et al. Antimicrobial activities and preliminary phytochemical tests of crude extracts of important ethnopharmacological plants from Brazilian Cerrado. J Med Plants Res 2016; 10: 612-20.
[16]
Scarpa GF. Medicinal plants used by the Criollos of Northwestern Argentine Chaco. J Ethnopharmacol 2004; 91: 115-35.
[17]
Petenatti EM, Gette MA, Derita M, et al. Importance of the ethnomedical information for the detection of antifungal properties in plant extracts form Argentine flora. In: Martino V, Muschietti L, Eds South American plants as a potential source of bioactive compounds. Kerala: Transworld Res Net 2008; pp. 15-38.
[18]
Estomba D, Ladio A, Lozada M. Medicinal wild plant knowledge and gathering patterns in a Mapuche community from North-western Patagonia. J Ethnopharmacol 2006; 103: 109-19.
[19]
Goleniowski ME, Bongiovanni GA, Palacio L, et al. Medicinal plants from the “Sierra de Comechingones”, Argentina. J Ethnopharmacol 2006; 107: 324-41.
[20]
Svetaz L, Zuljan F, Derita M, et al. Value of the ethnomedical information for the discovery of plants with antifungal properties. A survey among seven Latin American countries. J Ethnopharmacol 2010; 127: 137-58.
[21]
Martínez GJ, Barboza GE. Natural pharmacopoeia used in traditional Toba medicine for the treatment of parasitosis and skin disorders (Central Chaco, Argentina). J Ethnopharmacol 2010; 132: 86-100.
[22]
CLSI Reference method for broth dilution antifungal susceptibility testing of yeasts Approved Standard Document M27-A3 Wayne: Clinical Laboratory Standards Institute 2008; pp. 25.
[23]
Zhang L, Yan K, Zhang Y, et al. High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections. Proc Natl Acad Sci 2007; 104: 4606-11.
[24]
Chen X, Ren B, Chen M, et al. NLLSS: predicting synergistic drug combinations based on semi-supervised learning. PLOS Comput Biol 2016; 12: e1004975.
[25]
Williams DW, Jordan RP, Wei XQ, et al. Interactions of Candida albicans with host epithelial surfaces. J Oral Microbiol 2013; 5: 22434.
[26]
Lewis RE. Overview of the changing epidemiology of candidemia. Curr Med Res Opin 2009; 25: 1732-40.
[27]
Pfaller M, Diekema D. Epidemiology of invasive candidiasis: A persistent public health problem. Clin Microbiol Rev 2007; 20: 133-63.
[28]
Gudlaugsson O, Gillespie S, Lee K, et al. Attributable mortality of nosocomial candidemia, revised. Clin Infect Dis 2003; 37: 1172-7.
[29]
Chowdhary A, Sharma C, Meis JF. Candida auris: A rapidly emerging cause of hospital-acquired multidrug- resistant fungal infections globally. PLoS pathogen 2017; 13: e1006290.
[30]
Svetaz LA, Postigo A, Butassi E, et al. Antifungal drugs combinations: a patent review 2000-2015. Expert Opin Ther Pat 2016; 26: 439-53.