Avaliação da atividade antifúngica de plantas nativas do Brasil frente às linhagens de Cryptococcus e Candida

Abstract

Medicinal plants play a crucial role in drug discovery, providing bioactive compounds with therapeutic properties while emphasizing the importance of biodiversity preservation. Studying plants as sources of antimicrobial molecules represents an innovative strategy for health promotion. Anacardium occidentale and Myracrodruon urundeuva, both belonging to the Anacardiaceae family, are known for their ethnopharmacological uses and established antibacterial activity. The aim of this study was to evaluate the antimicrobial activity of native plants in vitro and in vivo against Cryptococcus and Candida species. The initial phase of the study involved a screening of native plants through the minimum inhibitory concentration (MIC) test. After this initial screening, A. occidentale and M. urundeuva emerged as the most promising Candidates for further investigation. In the next phase, the ethyl acetate fraction obtained from the ethanolic extracts of A. occidentale (FAAo) and M. urundeuva (FAMu) was selected for subsequent testing. Both fractions were then assessed for their anti-Candida and anti-Cryptococcus activities in vitro, through the determination of MIC and minimum fungicidal concentration (MFC). Following this, the death kinetics and the ability to inhibit biofilm formation of FAAo were evaluated. Assays were also conducted to understand the mechanism of action of FAMu against Cryptococcus strains, including the evaluation of ergosterol content, lipid peroxidation (measured by thiobarbituric acid reactive substances, TBARS), antioxidant system activity, and changes in cell diameter. In addition, in vivo infection assays were performed using Tenebrio molitor larvae. FAAo demonstrated MICs lower than 10 μg/mL for all tested Candida strains and was able to reduce biofilm formation in C. krusei ATCC 6258 and C. albicans ATCC 10231 at low concentrations. Phenolic compounds from FAMu exhibited antifungal activity in vitro against Candida and Cryptococcus, with a dose-dependent effect against all tested strains. FAMu altered ergosterol content, induced lipid peroxidation, modified the Cryptococcus capsule, and influenced the cell surface charge, increasing fungal vulnerability. In vivo assays with T. molitor showed that FAMu had low toxicity and, in combination with fluconazole, enhanced the survival of larvae infected with C. neoformans, indicating its efficacy in controlling the infection. Based on these results, we conclude that FAAo exhibits activity against Candida and Cryptococcus strains in vitro, suggesting its potential to inhibit biofilm formation by C. albicans, a major opportunistic pathogen in invasive infections. Our findings also indicate that FAMu demonstrates promising antifungal activity in vitro and in vivo against Cryptococcus strains, highlighting its potential as a source for the discovery of lead compounds in the development of new antifungal molecules. These fractions may expand the antifungal arsenal, offering effective alternatives for controlling resistant pathogens and improving available therapeutic options, either as standalone treatments or in combination with conventional antifungals.