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<p>More than half a century after the introduction of amphotericin B, the cryptococcosis treatment remains unsatisfactory. This disease, caused by yeasts of the genus <i>Cryptococcus</i>, is responsible for a considerable mortality rate and morbidity, mainly due to the adverse effects arising from the treatment which is limited to amphotericin B used in combination with other antifungals, such as voriconazole. Due to these factors, therapeutic alternatives have been investigated, either by association with other classes of antifungals or by combination with natural compounds. Propolis is a complex resinous mixture produced by bees and its antimicrobial activity has been intensely investigated. Among the different types of propolis, Brazilian red propolis has been shown antifungal activity. However, little is known about its anti-<i>Cryptococcus</i> activity. The objective of this study was to investigate the ability of the <i>n</i>-hexane extract of Brazilian red propolis (hex-BRP), containing polyprenylated benzophenones, to act against clinical strains of <i>Cryptococcus neoformans</i> and analyze the synergism with amphotericin B through the checkerboard method. The <i>n</i>-hexane extract exhibited minimal inhibitory concentrations between 7.81 and 1.95&#xa0;μg/ml. The <i>n</i>-hexane extract and amphotericin B showed synergy and additivity against four strains of <i>Cryptococcus neoformans</i>. These findings point to hex-BRP as an important therapeutic strategy, since it caused a reduction in the dose of amphotericin B from 0.125 to 0.031&#xa0;μg/ml. It is worth mentioning that these results are promising and the activity was superior to that demonstrated by the classic combination with flucytosine.</p> Graphical Abstract <p></p>

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Anti-Cryptococcal Synergistic Activity of the Association Between Amphotericin B and n-hexane Extract from Brazilian Red Propolis

  • 期刊论文

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  • 发表日期：

    2026年6月1日

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  • Eduardo Balbueno,
  • Camila Hatwig,
  • Bruna Pippi,
  • Alexandre Fuentefria,
  • Gilsane Lino von Poser

摘要

More than half a century after the introduction of amphotericin B, the cryptococcosis treatment remains unsatisfactory. This disease, caused by yeasts of the genus Cryptococcus, is responsible for a considerable mortality rate and morbidity, mainly due to the adverse effects arising from the treatment which is limited to amphotericin B used in combination with other antifungals, such as voriconazole. Due to these factors, therapeutic alternatives have been investigated, either by association with other classes of antifungals or by combination with natural compounds. Propolis is a complex resinous mixture produced by bees and its antimicrobial activity has been intensely investigated. Among the different types of propolis, Brazilian red propolis has been shown antifungal activity. However, little is known about its anti-Cryptococcus activity. The objective of this study was to investigate the ability of the n-hexane extract of Brazilian red propolis (hex-BRP), containing polyprenylated benzophenones, to act against clinical strains of Cryptococcus neoformans and analyze the synergism with amphotericin B through the checkerboard method. The n-hexane extract exhibited minimal inhibitory concentrations between 7.81 and 1.95 μg/ml. The n-hexane extract and amphotericin B showed synergy and additivity against four strains of Cryptococcus neoformans. These findings point to hex-BRP as an important therapeutic strategy, since it caused a reduction in the dose of amphotericin B from 0.125 to 0.031 μg/ml. It is worth mentioning that these results are promising and the activity was superior to that demonstrated by the classic combination with flucytosine.

Graphical Abstract