Honokiol and Magnolol: Insights into Their Antidermatophytic Effects

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...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Plants
Subjects:
Online Access:https://www.mdpi.com/2223-7747/10/11/2522
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author 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_facet 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_sort Adriana Trifan
collection DOAJ
description 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 <i>Magnolia</i> 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 <i>Trichophyton rubrum</i> cells by HPLC-DAD. Putative interactions with terbinafine against <i>T. rubrum</i> 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 <i>T. rubrum</i> 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.
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spelling doaj.art-cd746badca4945eabc3589a5222f07072023-11-23T01:07:12ZengMDPI AGPlants2223-77472021-11-011011252210.3390/plants10112522Honokiol and Magnolol: Insights into Their Antidermatophytic EffectsAdriana Trifan0Andra-Cristina Bostănaru1Simon Vlad Luca2Veronika Temml3Muhammad Akram4Sonja Herdlinger5Łukasz Kulinowski6Krystyna Skalicka-Woźniak7Sebastian Granica8Monika E. Czerwińska9Aleksandra Kruk10Hélène Greige-Gerges11Mihai Mareș12Daniela Schuster13Department of Pharmacognosy, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700115 Iasi, RomaniaLaboratory of Antimicrobial Chemotherapy, Faculty of Veterinary Medicine, “Ion Ionescu de la Brad” Iasi University of Life Sciences, 700489 Iasi, RomaniaDepartment of Pharmacognosy, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700115 Iasi, RomaniaDepartment of Pharmaceutical Chemistry, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaDepartment of Pharmaceutical Chemistry, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaDepartment of Pharmaceutical Chemistry, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaDepartment of Natural Products Chemistry, Medical University of Lublin, 20-093 Lublin, PolandDepartment of Natural Products Chemistry, Medical University of Lublin, 20-093 Lublin, PolandMicrobiota Lab, Centre for Preclinical Studies, Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, 02-097 Warsaw, PolandDepartment of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, PolandMicrobiota Lab, Centre for Preclinical Studies, Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, 02-097 Warsaw, PolandBioactive Molecules Research Laboratory, Department of Chemistry and Biochemistry, Faculty of Sciences, Section II, Lebanese University, Jdeidet el-Matn B.P. 90656, LebanonLaboratory of Antimicrobial Chemotherapy, Faculty of Veterinary Medicine, “Ion Ionescu de la Brad” Iasi University of Life Sciences, 700489 Iasi, RomaniaDepartment of Pharmaceutical Chemistry, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaDermatophyte 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 <i>Magnolia</i> 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 <i>Trichophyton rubrum</i> cells by HPLC-DAD. Putative interactions with terbinafine against <i>T. rubrum</i> 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 <i>T. rubrum</i> 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.https://www.mdpi.com/2223-7747/10/11/2522ergosterolcheckerboard assaycytokinessqualenesynergyterbinafine
spellingShingle 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
Honokiol and Magnolol: Insights into Their Antidermatophytic Effects
Plants
ergosterol
checkerboard assay
cytokines
squalene
synergy
terbinafine
title Honokiol and Magnolol: Insights into Their Antidermatophytic Effects
title_full Honokiol and Magnolol: Insights into Their Antidermatophytic Effects
title_fullStr Honokiol and Magnolol: Insights into Their Antidermatophytic Effects
title_full_unstemmed Honokiol and Magnolol: Insights into Their Antidermatophytic Effects
title_short Honokiol and Magnolol: Insights into Their Antidermatophytic Effects
title_sort honokiol and magnolol insights into their antidermatophytic effects
topic ergosterol
checkerboard assay
cytokines
squalene
synergy
terbinafine
url https://www.mdpi.com/2223-7747/10/11/2522
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