Abstract
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.
Highlights
Dermatophytosis has emerged as an important public health issue, affecting up to25% of the global population [1]
[3], dermatophytes are classified into seven clades, with prevalence in clinical isolates of dermatophytes are classified into seven clades, with prevalence in clinical isolates of Trichophyton, Epidermophyton, Microsporum and Nannizzia genera
The minimal fungicidal concentration (MFC) values revealed that both honokiol and magnolol exhibited fungicidal activity against the tested dermatophytes (Table 1)
Summary
Dermatophytosis has emerged as an important public health issue, affecting up to25% of the global population [1]. Dermatophytes are filamentous fungi that invade the. Dermatophytes are filamentous fungi that invade the keratinized structures of the skin, hair and nails, causing infections with different degrees keratinized structures of the skin, hair and nails, causing infections with different degrees of inflammation among immunocompetent individuals [2]. [3], dermatophytes are classified into seven clades, with prevalence in clinical isolates of dermatophytes are classified into seven clades, with prevalence in clinical isolates of Trichophyton, Epidermophyton, Microsporum and Nannizzia genera. Trichophyton species repTrichophyton, Epidermophyton, Microsporum and Nannizzia genera. The search for novel antifungal agents taremergence of fungal resistance [5,6]. The search for novel antifungal agents geting structures that areare unique to to dermatophytes is highly imperative
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
