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
Author Information
Adriana Trifan: Department of Pharmacognosy, Faculty of Pharmacy, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania. ORCID
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. 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, Jdeidet el-Matn B.P. 90656, Lebanon. 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
Daniela Schuster: Department of Pharmaceutical Chemistry, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria. ORCID
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 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 cells by HPLC-DAD. Putative interactions with terbinafine against 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 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.
