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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ergosterol checkerboard assay cytokines squalene synergy terbinafine Botany QK1-989
Acceso en línea:	https://doaj.org/article/cd746badca4945eabc3589a5222f0707
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spelling	oai:doaj.org-article:cd746badca4945eabc3589a5222f07072021-11-25T18:47:22ZHonokiol and Magnolol: Insights into Their Antidermatophytic Effects10.3390/plants101125222223-7747https://doaj.org/article/cd746badca4945eabc3589a5222f07072021-11-01T00:00:00Zhttps://www.mdpi.com/2223-7747/10/11/2522https://doaj.org/toc/2223-7747Dermatophyte 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.Adriana TrifanAndra-Cristina BostănaruSimon Vlad LucaVeronika TemmlMuhammad AkramSonja HerdlingerŁukasz KulinowskiKrystyna Skalicka-WoźniakSebastian GranicaMonika E. CzerwińskaAleksandra KrukHélène Greige-GergesMihai MareșDaniela SchusterMDPI AGarticleergosterolcheckerboard assaycytokinessqualenesynergyterbinafineBotanyQK1-989ENPlants, Vol 10, Iss 2522, p 2522 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ergosterol checkerboard assay cytokines squalene synergy terbinafine Botany QK1-989
spellingShingle	ergosterol checkerboard assay cytokines squalene synergy terbinafine Botany QK1-989 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
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.
format	article
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
title	Honokiol and Magnolol: Insights into Their Antidermatophytic Effects
title_short	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_sort	honokiol and magnolol: insights into their antidermatophytic effects
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cd746badca4945eabc3589a5222f0707
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Honokiol and Magnolol: Insights into Their Antidermatophytic Effects

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