Brazilian Copaifera Species: Antifungal Activity against Clinically Relevant Candida Species, Cellular Target, and In Vivo Toxicity.

Géssica Andrade,Fariza Abrão,Haniel Orlando,Regina Pires,Rodrigo Veneziani,Reginaldo Pedroso,Marco Carvalho,Jairo Bastos,Carlos Martins,Liliana Scorzoni,Sérgio Ambrósio,Maria Mendes-Giannini

doi:10.3390/jof6030153

Abstract

Plants belonging to the genus Copaifera are widely used in Brazil due to their antimicrobial properties, among others. The re-emergence of classic fungal diseases as a consequence of antifungal resistance to available drugs has stimulated the search for plant-based compounds with antifungal activity, especially against Candida. The Candida-infected Caenorhabditis elegans model was used to evaluate the in vitro antifungal potential of Copaifera leaf extracts and trunk oleoresins against Candida species. The Copaifera leaf extracts exhibited good antifungal activity against all Candida species, with MIC values ranging from 5.86 to 93.75 µg/mL. Both the Copaifera paupera and Copaifera reticulata leaf extracts at 46.87 µg/mL inhibited Candida glabrata biofilm formation and showed no toxicity to C. elegans. The survival of C. glabrata-infected nematodes increased at all the tested extract concentrations. Exposure to Copaifera leaf extracts markedly increased C. glabrata cell vacuolization and cell membrane damage. Therefore, Copaifera leaf extracts are potential candidates for the development of new and safe antifungal agents.

Highlights

Modern medicine is well developed in most parts of the world, WHO recognizes that a large part of the population in developing countries depends on traditional medicine for primary care [1]
In view of the emergence of resistant strains and the expansion of fungal virulence mechanisms, we evaluate the Candida species susceptibility profile against Copaifera species extracts and oleoresins by determining their minimal inhibitory concentration values, their ability to inhibit biofilm formation, and their effect when associated with amphotericin B
The leaf extracts were prepared by macerating the ground air-dried C. duckei, C. langsdorffii, C. lucens, C. multijuga, C. oblongifolia, C. paupera, C. reticulata, and C. trapezifolia leaves in 7:3 ethanol/water at room temperature for 48 h

Summary

Introduction

Modern medicine is well developed in most parts of the world, WHO recognizes that a large part of the population in developing countries depends on traditional medicine for primary care [1] In this regard, Brazil is the most biodiverse country on the planet and holds valuable traditional knowledge associated with the use of medicinal plants [2]. J. Fungi 2020, 6, 153; doi:10.3390/jof6030153 www.mdpi.com/journal/jof. Copaifera (Leguminosae Juss., subfamily Caesalpinoideae Kunth) is a genus of large trees that comprises more than 72 species occurring in Latin America, India, and West Africa. Sixteen of these species are found only in Brazil, mainly in the northern and northeastern regions, in the states of Amazonas, Pará, and Ceará [3,4]. Plant derivatives such as oleoresins and essential oils are widely employed in folk medicine; the use of leaf extracts is less common, but some reports have demonstrated their antiurolithiac, antiedematogenic, and gastroprotective potential, which were mostly related to the presence of galloylquinic acid derivatives and flavonoids [5,6,7]

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