Atividade antifúngica dos óleos essenciais das folhas de Citrus limon (L.) Burm. f. e Citrus sinensis (L.) Osbeck contra cep as de Candida albicans na forma planctônica e de biofilme

Abstract

Candida albicans is an opportunistic pathogen that can cause infections in its host through its virulence factors. The limited antifungal options have led to a search for therapeutic alternatives, and essential oils, such as those from the Citrus genus, stand out for their antifungal potential. The study was conducted in the northern region of the state of Ceará, through partnerships between institutions. It strengthens regional innovation and the potential of bioprospecting natural products in microbiology using plants cultivated in the region, thus presenting important results in the areas of biotechnology and health. This study analyzes the chemical composition, antifungal activity against Candida albicans in planktonic and biofilm forms, cytotoxicity in human erythrocytes, and pharmacokinetic properties of essential oils from Citrus limon and Citrus sinensis. The essential oils were extracted from the leaves by hydrodistillation, and their composition was verified by GC-MS. Antifungal activity was evaluated using broth microdilution and death kinetics. Combined effects were assessed using the Checkerboard method, while antibiofilm tests were evaluated using plate assays and microscopy . Hemolytic activity tests were performed using a percentage of hemolysis. The essential oils contain limonene (40.81-36.69%) as the major constituent. The Minimum Inhibitory Concentration was 0.312–1.25 mg/mL, with a killing kinetic of up to 10 h. It showed additive (C. limon/fluconazole) and synergistic (C. sinensis/fluconazole) effects. It exhibited anti-adhesion and anti-polymorphism effects, initiating biofilm formation. It also exhibited low cytotoxicity , with an LC50 of 14,000-13,000 μg/mL. ADMET and BOILED-Egg pharmacokinetic predictions indicated safety for systemic use. Both essential oils exhibited strong anti-Candida activity with minimal cytotoxicity . Their additive/synergistic effects with fluconazole highlight their potential as an alternative or adjuvant therapy against C. albicans infections.