Pharmacological potential of limonene against opportunistic fungi: Impact on Candida virulence

• Published in: Acta tropica 2024-05, Vol.253, p.107168-107168, Article 107168
• Main Authors: novais, Maria Hellena Garcia, farias, Naiza Saraiva, Dos santos, Andressa Guilhermino, fonseca, Victor Juno Alencar, Ribeiro-Filho, Jaime, De menezes, Irwin Rose Alencar, Coutinho, Henrique Douglas Melo, Morais-Braga, Maria Flaviana Bezerra
• Format: Article
• Language: English
• Subjects: antimicrobial properties; Candida; fluconazole; fungal growth; Fungi; gene expression; growth retardation; hyphae; Limonene; medicine; minimum inhibitory concentration; multiple drug resistance; species; statistical analysis; therapeutics; Virulence; yeasts
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/j.actatropica.2024.107168

•Limonene has antifungal effects against different strains of Candida.•Limonene potentiated the activity of fluconazole.•Limonene has antifungal activity associated with decreased resistance to antifungals. The present article aims to evaluate the antifungal and antivirulence effect of the phytoconstituent Limonene against Candida spp. Antifungal assays were performed, where the concentration capable of inhibiting 50 % of fungal growth, the growth inhibition curve, the minimum fungicidal concentration, the evaluation of the modifying effect with fluconazole, the inhibitory effect of the substances on the morphological transition of Candida spp. and the statistical analysis of the results were determined. With this study, it was seen that limonene demonstrated growth inhibition for the strains tested and when associated the natural compound with Fluconazole, there was potentiation of the effect of the drug, since the inhibition of growth by the combination occurred at lower concentrations against all strains tested, when compared to the drug alone, which inhibited growth at the highest concentration. In the test to determine the Minimum Fungicidal Concentration of the products tested alone and in combination, it was found that in the case of Candida strains, growth inhibition by limonene occurred at a concentration of 1024 μg/mL. For Fluconazole, growth impairment ranged from > 1024 μg/mL to 256 μg/mL for the strains. And when combined, limonene potentiated the action of FCZ, making fungal colonization unfeasible at concentrations below 1024 μg/mL. Regarding the morphological transition from yeast to hyphae, limonene was used at concentrations of 1024 μg/mL and 512 μg/mL, and it was found that, for CA and CK, the filaments were reduced in number and size at the highest concentration and against CT, the morphological transition from yeast to hyphae/pseudohyphae was totally inhibited, and if compared to the growth control, limonene was able to reduce fungal growth at concentrations greater than 512 μg/mL. This compound has antimicrobial activity described, due to its ability to interfere in the gene expression of the fungus, the limited therapeutic options and the recent emergence of multidrug-resistant Candida species represent a significant challenge for human medicine and highlight the need for new therapeutic approaches, and in this study a great potential of limonene was revealed in relation to the perspective of increasing the efficiency of commercial d