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
Author Information
Adriana Trifan: Department of Pharmacognosy, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania. ORCID
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. ORCID
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. ORCID
Krystyna Skalicka-Woźniak: Department of Natural Products Chemistry, Medical University of Lublin, 20-093 Lublin, Poland. ORCID
Sebastian Granica: Microbiota Lab, Centre for Preclinical Studies, Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, 02-097 Warsaw, Poland. ORCID
Monika E Czerwińska: Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland. ORCID
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. ORCID
Elwira Sieniawska: Department of Natural Products Chemistry, Medical University of Lublin, 20-093 Lublin, Poland. ORCID
Mihai Mareș: Laboratory of Antimicrobial Chemotherapy, Faculty of Veterinary Medicine, "Ion Ionescu de la Brad" Iasi University of Life Sciences, 700489 Iasi, Romania. ORCID
Dermatophyte infections represent an important public health concern, affecting up to 25% of the world's population. and 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 ATCC 28188 and 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-1, IL-8 and TNF-) was determined using an ex vivo human neutrophils model. The binary associations of tested EOs with terbinafine were found to be synergistic against , 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-1 release (46.49% inhibition at 25 mg/L), while coriander EO displayed the highest inhibition towards IL-8 and TNF- 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 -related dermatophytosis.
