Casearia sylvestris essential oil and its fractions inhibit Candida albicans ABC transporters related to multidrug resistance (MDR)

Abstract

ABC transporters constitute a superfamily of transmembrane proteins that act mediating the translocation of several substrates across the membrane, using the energy of ATP hydrolysis. This mechanism of unrelated substrates efflux (multidrug resistance) has been associated with several diseases and it is a problem in chemotherapy efficacy. Nowadays, approximately 25% of the prescription drugs in the world are derived from plants. Casearia sylvestris is commonly found in the Americas and different parts of this plant are popularly used to treat several diseases. Previous studies have also confirmed the biological activities of C. sylvestris, such as anti-tumor, anti-leishmania, and antifungal properties. Then, the propose of this study was demonstrate that fraction 1-6 of C. sylvestris, essential oil, was able to reverse the fluconazole resistance phenotype in the Saccharomyces cerevisiae model mediated by the heterologous protein CaCdr2p from Candida albicans. The MIC value of fraction 1-6 combined with fluconazole in the checkerboard assay decreased approximately 4-fold, suggesting a synergistic effect. In addition, fraction 1-6 increased intracellular rhodamine 6G accumulation from 17% to 49% in the presence of glucose. Data indicate that C. sylvestris fraction 1-6 is a potential reverser of the fluconazole resistance phenotype.

Casearia Essential Oil: An Updated Review on the Chemistry and Pharmacological Activities

“…Fraction 1-6 plus fluconazole showed MIC at 12.5 μg/mL indicating synergism between fraction 1-6 and fluconazole according to a fractional inhibition concentration index of 0.48 (< 0.5). [46] The MIC values for plant derivatives are used to classify antifungal activity levels: lower than 100 μg/mL is defined as significantly active, whereas from 100 to 625 μg/mL is moderately active, and greater than 625 μg/mL is weak active. [55] Thus, EO activity against S. cerevisiae and Candida species were significantly and moderately active, respectively, while fraction 1-6 of the C. sylvestris showed a significant activity.…”

“…Fraction 1–6 presented the total inhibition of cell growth against strain CaCDR1 of the C. albicans with MIC at 50.0 μg/mL, while fluconazole MIC was 75.0 μg/mL. Fraction 1–6 plus fluconazole showed MIC at 12.5 μg/mL indicating synergism between fraction 1–6 and fluconazole according to a fractional inhibition concentration index of 0.48 (<0.5) [46] …”