Abstract:
Dermatophyte infections represent an important public health concern, affecting up to 25%
of the world’s population. Trichophyton rubrum and T. mentagrophytes are the predominant dermatophytes
in cutaneous infections, with a prevalence accounting for 70% of dermatophytoses. Although
terbinafine represents the preferred treatment, its clinical use is hampered by side effects, drug–
drug interactions, and the emergence of resistant clinical isolates. Combination therapy, associating
terbinafine and essential oils (EOs), represents a promising strategy in the treatment of dermatophytosis.
In this study, we screened the potential of selected Apiaceae EOs (ajowan, coriander, caraway,
and anise) to improve the antifungal activity of terbinafine against T. rubrum ATCC 28188 and T. mentagrophytes
ATCC 9533. The chemical profile of EOs was analyzed by gas chromatography. The
minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of EOs/main
compounds were determined according to EUCAST-AFST guidelines, with minor modifications. The
checkerboard microtiter method was used to identify putative synergistic combinations of EOs/main
constituents with terbinafine. The influence of EOs on the viability and pro-inflammatory cytokine
production (IL-1b, IL-8 and TNF-a) was determined using an ex vivo human neutrophils model. The
binary associations of tested EOs with terbinafine were found to be synergistic against T. rubrum,
with FICI values of 0.26–0.31. At the tested concentrations (6.25–25 mg/L), EOs did not exert cytotoxic
effects towards human neutrophils. Anise EO was the most potent inhibitor of IL-1b release
(46.49% inhibition at 25 mg/L), while coriander EO displayed the highest inhibition towards IL-8
and TNF-a production (54.15% and 54.91%, respectively). In conclusion, the synergistic combinations
of terbinafine and investigated Apiaceae EOs could be a starting point in the development of novel
topical therapies against T. rubrum-related dermatophytosis.
