Honokiol and Magnolol: Insights into Their Antidermatophytic Effects
Adriana Trifan,
Andra-Cristina Bostănaru,
Simon Vlad Luca,
Veronika Temml,
Muhammad Akram,
Sonja Herdlinger,
Łukasz Kulinowski,
Krystyna Skalicka-Woźniak,
Sebastian Granica,
Monika E. Czerwińska,
Aleksandra Kruk,
Hélène Greige-Gerges,
Mihai Mareș,
Daniela Schuster
Affiliations
Adriana Trifan
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
Simon Vlad Luca
Department of Pharmacognosy, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
Veronika Temml
Department of Pharmaceutical Chemistry, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
Muhammad Akram
Department of Pharmaceutical Chemistry, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
Sonja Herdlinger
Department of Pharmaceutical Chemistry, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
Łukasz Kulinowski
Department of Natural Products Chemistry, Medical University of Lublin, 20-093 Lublin, Poland
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, Jdeidet el-Matn B.P. 90656, Lebanon
Mihai Mareș
Laboratory of Antimicrobial Chemotherapy, Faculty of Veterinary Medicine, “Ion Ionescu de la Brad” Iasi University of Life Sciences, 700489 Iasi, Romania
Daniela Schuster
Department of Pharmaceutical Chemistry, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
Dermatophyte infections represent a significant public health concern, with an alarming negative impact caused by unsuccessful therapeutic regimens. Natural products have been highlighted as a promising alternative, due to their long-standing traditional use and increasing scientific recognition. In this study, honokiol and magnolol, the main bioactives from Magnolia spp. bark, were investigated for their antidermatophytic activity. The antifungal screening was performed using dermatophyte standard strains and clinical isolates. The minimal inhibitory concentration (MIC) and the minimal fungicidal concentration (MFC) were determined in accordance with EUCAST-AFST guidelines, with minor modifications. The effects on ergosterol biosynthesis were assessed in Trichophyton rubrum cells by HPLC-DAD. Putative interactions with terbinafine against T. rubrum were evaluated by the checkerboard method. Their impact on cells’ viability and pro-inflammatory cytokines (IL-1β, IL-8 and TNF-α) was shown using an ex vivo human neutrophils model. Honokiol and magnolol were highly active against tested dermatophytes, with MIC and MFC values of 8 and 16 mg/L, respectively. The mechanism of action involved the inhibition of ergosterol biosynthesis, with accumulation of squalene in T. rubrum cells. Synergy was assessed for binary mixtures of magnolol with terbinafine (FICI = 0.50), while honokiol-terbinafine combinations displayed only additive effects (FICI = 0.56). In addition, magnolol displayed inhibitory effects towards IL-1β, IL-8 and TNF-α released from lipopolysaccharide (LPS)-stimulated human neutrophils, while honokiol only decreased IL-1β secretion, compared to the untreated control. Overall, honokiol and magnolol acted as fungicidal agents against dermatophytes, with impairment of ergosterol biosynthesis.
