Apiaceae Essential Oils: Boosters of Terbinafine Activity against Dermatophytes and Potent Anti-Inflammatory Effectors
Adriana Trifan,
Simon Vlad Luca,
Andra-Cristina Bostănaru,
Mihai Brebu,
Alexandra Jităreanu,
Romeo-Teodor Cristina,
Krystyna Skalicka-Woźniak,
Sebastian Granica,
Monika E. Czerwińska,
Aleksandra Kruk,
Hélène Greige-Gerges,
Elwira Sieniawska,
Mihai Mareș
Affiliations
Adriana Trifan
Department of Pharmacognosy, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
Simon Vlad Luca
Department of Pharmacognosy, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
Andra-Cristina Bostănaru
Laboratory of Antimicrobial Chemotherapy, Faculty of Veterinary Medicine, “Ion Ionescu de la Brad” Iasi University of Life Sciences, 700489 Iasi, Romania
Mihai Brebu
Physical Chemistry of Polymers Laboratory, Petru Poni Institute of Macromolecular Chemistry, 700481 Iasi, Romania
Alexandra Jităreanu
Department of Toxicology, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
Romeo-Teodor Cristina
Department of Pharmacology, The Banat University of Agricultural Sciences and Veterinary Medicine, 300645 Timisoara, Romania
Krystyna Skalicka-Woźniak
Department of Natural Products Chemistry, Medical University of Lublin, 20-093 Lublin, Poland
Sebastian Granica
Microbiota Lab, Centre for Preclinical Studies, Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, 02-097 Warsaw, Poland
Monika E. Czerwińska
Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland
Aleksandra Kruk
Microbiota Lab, Centre for Preclinical Studies, Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, 02-097 Warsaw, Poland
Hélène Greige-Gerges
Bioactive Molecules Research Laboratory, Department of Chemistry and Biochemistry, Faculty of Sciences, Section II, Lebanese University, Jdaidet el-Matn B.P. 90656, Lebanon
Elwira Sieniawska
Department of Natural Products Chemistry, Medical University of Lublin, 20-093 Lublin, Poland
Mihai Mareș
Laboratory of Antimicrobial Chemotherapy, Faculty of Veterinary Medicine, “Ion Ionescu de la Brad” Iasi University of Life Sciences, 700489 Iasi, Romania
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.
