Apiaceae Essential Oils: Boosters of Terbinafine Activity against Dermatophytes and Potent Anti-Inflammatory Effectors

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-1β, IL-8 and TNF-α) 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-1β release (46.49% inhibition at 25 mg/L), while coriander EO displayed the highest inhibition towards IL-8 and TNF-α 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.

Emerging Biopharmaceuticals from Pimpinella Genus

“…In another dermatophyte infections study [ 96 ], combined treatment with terbinafine and P. anisum oil showed that oil enhanced the activity of terbinafine against Trichophytonrubrum and T. mentagrophytes with a 4-fold reduction in the MIC. The combination therapy had a synergistic effect on reducing the concentration of antifungal drugs and the appearance of resistant strains than monotherapy.…”

Cassia alata, Coriandrum sativum, Curcuma longa and Azadirachta indica: Food Ingredients as Complementary and Alternative Therapies for Atopic Dermatitis-A Comprehensive Review

“…The expression of IL-1 β , IL-6, and TNF- α was suppressed or lowered upon treatment with C. sativum extract, oil, and fractions. The suppression of inflammatory mediators was shown in the in vitro models such as lipopolysaccharide (LPS)-stimulated neutrophils [ 70 ], LPS-induced BV-2 microglia cells [ 71 ], LPS-stimulated RAW264.7 macrophage cells [ 72 , 73 ], and human bronchial epithelial cells [ 74 ]. The anti-inflammatory activities of C. sativum had also been investigated using various in vivo models.…”

Phytochemical Characterization and Evaluation of the Antioxidant and Anti-Enzymatic Activity of Five Common Spices: Focus on Their Essential Oils and Spent Material Extractives

“…TRB-5MS capillary columns (30 m length, 0.25 mm internal diameter, 0.25 µm film thickness) were used for each detector. The analysis was conducted according to a previously described method [94]. Retention indices were calculated for the individual compounds using a standard mixture of C8-C20 n-alkanes.…”

“…Retention indices were calculated for the individual compounds using a standard mixture of C8-C20 n-alkanes. The compounds from the essential oils were identified by comparison of their mass spectra with those from the NIST 11 Mass Spectra Library, and their retention indices with literature data (NIST Chemistry WebBook; [94,95]). The relative percentages of individual compounds were obtained from the FID peak areas without using correction factors.…”