Honokiol and Magnolol: Insights into Their Antidermatophytic Effects

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.

Recent developments on the anti-Candida effect of amphotericin B combined with a second drug - a mini-review

“…Usually, synergistic (one drug enhances the activity of another), indifferent (drugs do not enhance each other activity), and antagonistic (one drug decreases the activity of another) interactions are defined by FICI ≤0.5, >0.5 -4.0, and > 4.0, respectively (Odds 2003). There are some studies that consider an extra type of interaction, namely "additive", when FICI value is between 0.5 and 1.0 (Trifan et al 2021). The combinatory antifungal activity may also be determined by adding a specific concentration of drug A to different concentrations of drug B, generally obtained by serial dilution.…”

Emerging Antifungal Targets and Strategies

“…Apigenin, rutin, and palmitic acid downregulated the expression of ERG11 [ 56 , 104 ]. Other studies targeted ergosterol biosynthesis by applying tormentic acid [ 105 ], benzodioxane derivatives [ 106 ], honokiol and magnolol [ 107 ], and cold atmospheric plasma [ 108 ].…”

The application prospects of honokiol in dermatology

“…Recently, it had been reported that honokiol inhibited the common standard strains and clinical strains of dermatophytes by destroying the ergosterol biosynthesis. And it enhanced the terbinafine's activity against Trichophyton rubrum 12 . Honokiol could also be used against other bacteria or viruses associating with skin diseases, for example, Propionibacterium acnes 13 and Herpes Simplex Virus‐1 14 …”