Frontiers in pharmacology · 2026
In vitro and in vivo antifungal effects of fluconazole in combination with Cinnamomum verum essential oil against Candida spp.
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Nedea Marina Ionela, Velicu Serena-Ștefania, Marinaş Ioana Cristina, Buleandră Mihaela, Letiția Arsene Andreea, Velescu Bruno Ștefan, Chifiriuc Mariana Carmen, Gheorghe-Barbu Irina
Аннотация
INTRODUCTION: Antifungal resistance in Candida species is a growing clinical problem globally, especially in immunocompromised patients. One of the alternative approaches to conventional therapies are currently based on essential oils (EOs) alone or in combination with antifungals. We aimed to evaluate the antifungal activity of Cinnamomum verum EO, alone and in combination with fluconazole, against reference and multidrug-resistant (MDR) Candida strains by in vitro and in vivo assays.
METHODS: The chemical composition of the EO was analyzed by gas chromatography-mass spectrometry. Antifungal activity was assessed by broth microdilution (minimum inhibitory concentration determination), while anti-adherence effects were evaluated using the microtitration with crystal violet. The fractional inhibitory concentration index and response surface approach were used to study synergistic interactions. The in vivo efficacy was assessed by tracking virulence factors, fungal load, and larval survival in Galleria mellonella model.
RESULTS: The most significant phenylpropanoid components of the EO were (E)-cinnamaldehyde and eugenol. It demonstrated high antifungal activity and significantly decreased adherence to the inert substratum. The tested EO exhibited pharmacological synergy in combination with fluconazole, especially against fluconazole-resistant Candida auris strains. The optimized fluconazole-EO combination decreased fungal virulence and load, as well as G. mellonella larval mortality.
CONCLUSION: C. verum EO exhibits strong anti-virulence and antifungal effects and increases fluconazole activity, indicating its potential as an adjuvant treatment against resistant Candida infections.
METHODS: The chemical composition of the EO was analyzed by gas chromatography-mass spectrometry. Antifungal activity was assessed by broth microdilution (minimum inhibitory concentration determination), while anti-adherence effects were evaluated using the microtitration with crystal violet. The fractional inhibitory concentration index and response surface approach were used to study synergistic interactions. The in vivo efficacy was assessed by tracking virulence factors, fungal load, and larval survival in Galleria mellonella model.
RESULTS: The most significant phenylpropanoid components of the EO were (E)-cinnamaldehyde and eugenol. It demonstrated high antifungal activity and significantly decreased adherence to the inert substratum. The tested EO exhibited pharmacological synergy in combination with fluconazole, especially against fluconazole-resistant Candida auris strains. The optimized fluconazole-EO combination decreased fungal virulence and load, as well as G. mellonella larval mortality.
CONCLUSION: C. verum EO exhibits strong anti-virulence and antifungal effects and increases fluconazole activity, indicating its potential as an adjuvant treatment against resistant Candida infections.