Antifungal activity, synergistic effect and mode of action of Caraway (Carum carvi L.) essential oil and carvone against Aspergillus fumigatus

Abstract

IntroductionCurrently available antifungal therapies often have limitations such as toxicity and the development of resistance. The aim of this study was to investigate the antifungal activity and mode of action of Caraway (Carum carvi L.) essential oil (EO) and its constituent carvone against A. fumigatus, a fungal pathogen responsible for invasive aspergillosis. MethodsCaraway EO was obtained by hydrodistillation, and its antifungal activity was assessed by the broth microdilution method according to the CLSI protocol. The ergosterol content of fungal mycelia was measured using a spectrophotometric method. The mode of action of Caraway EO was assessed by electron microscopy. The interaction between Caraway EO and two known antifungals, itraconazole and caspofungin, was evaluated by determining the fractional inhibitory concentration index (FICI). ResultsAt twofold dilutions ranging from 3.12 to 400 µg/mL, Caraway EO inhibited A. fumigatus growth by 10.27–100 %, with a minimum inhibitory concentration (MIC) of 200 µg/mL, while carvone inhibited fungal growth by 7.31–67.58 %, with an MIC of 400 µg/mL. The IC50 values of the Caraway EO and carvone were 56.09 and 47.68 μg/mL, respectively. Moreover, the minimum fungicidal concentration (MFC) of the Caraway EO was reported to be 400 μg/mL. Both Caraway EO and carvone significantly inhibited ergosterol biosynthesis in A. fumigatus. Caraway EO showed synergistic antifungal activity in combination with itraconazole (FICI=0.38) and additive antifungal activity (FICI=0.75) in combination with caspofungin. ConclusionCaraway EO and its constituent carvone showed strong antifungal activity against A. fumigatus by inhibiting ergosterol biosynthesis and destroying essential compartments of fungal mycelia, such as mitochondria. In addition, the combination of carvone with itraconazole or caspofungin had synergistic/additive effects, suggesting potential therapeutic efficacy for the treatment of A. fumigatus-related infections.