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Published on: December 5, 2020
Ellagic Acid Inhibits Trichophyton rubrum Growth via Affecting Ergosterol Biosynthesis and Apoptotic Induction
Zhi-Jian Li1, Amima Abula1, Abudumijiti Abulizi2
1Department of Toxicology Laboratory, Xinjiang Institute of Traditional Uyghur Medicine, Urumqi, Xinjiang 830049, China.
Background:
Trichophyton rubrum, among other dermatophytes, is a major causative agent for superficial dermatomycoses like onychomycosis and tinea pedis, especially among pediatric and geriatric populations. Ellagic acid (EA) and shikonin (SK) have been reported to have many bioactivities, including antifungal activity. However, the mechanism of EA and SK on Trichophyton rubrum has not yet been reported.
Objectives:
The purposes of this study were to evaluate the antifungal activities of EA and SK against Trichophyton rubrum and to illuminate the underlying action mechanisms.
Methods:
The effect of EA (64, 128, and 256 μg/mL) and SK (8, 4, and 2 μg/mL) on Trichophyton rubrum was investigated with different doses via detecting cell viability, ultrastructure with using a scanning electron microscope (SEM), cell apoptosis and necrosis by using the flow cytometry instrument technique (FCIT), and the ergosterol biosynthesis pathway-related fungal cell membrane key gene expressions in vitro.
Results:
SEM detection revealed that the T. rubrum cell surface was shrivelled, folded, and showed deformation and expansion, visible surface peeling, and broken hyphae, and cell contents overflowed after being treated with EA and SK; the cell apoptosis rate was significantly increased in dose-dependent manner after T. rubrum was treated with EA and SK; the qPCR results showed that mRNA expression of MEP4 and SUB1 was downregulated in EA- and SK-treated groups.
Conclusions:
Overall, our results revealed the underlying antifungal mechanism of EA and SK, which may be related to the destruction of the fungal cell membrane and inhibition of C14 demethylase and the catalytic rate of squalene cyclooxidase in the ergosterol biosynthesis pathway via downregulation of MEP4 and SUB1, suggesting that EA and SK have the potential to be developed further as a natural antifungal agent for clinical use.
Insights
Ellagic acid (EA) and shikonin (SK) demonstrate potent antifungal activity against Trichophyton rubrum by damaging cell membranes and inhibiting ergosterol biosynthesis. These natural compounds show promise for developing new antifungal treatments.
Area of Science:
- Mycology
- Natural Product Chemistry
- Dermatology
Background:
- *Trichophyton rubrum* is a primary cause of superficial fungal infections like onychomycosis and tinea pedis, particularly in vulnerable populations.
- Ellagic acid (EA) and shikonin (SK) are natural compounds with known bioactivities, including antifungal properties, but their specific mechanisms against *T. rubrum* remain unelucidated.
Purpose of the Study:
- To evaluate the antifungal efficacy of Ellagic acid (EA) and shikonin (SK) against *Trichophyton rubrum*.
- To elucidate the molecular mechanisms underlying the antifungal action of EA and SK.
Main Methods:
- Investigated the effects of varying doses of EA and SK on *T. rubrum* viability and cell structure using scanning electron microscopy (SEM).
- Assessed fungal cell apoptosis and necrosis via flow cytometry and analyzed the expression of key ergosterol biosynthesis pathway genes (e.g., MEP4, SUB1) using qPCR.
Main Results:
- SEM revealed significant damage to *T. rubrum* cell surfaces, including shrinkage, folding, peeling, and cell content leakage after EA and SK treatment.
- EA and SK significantly increased fungal cell apoptosis rates in a dose-dependent manner.
- qPCR analysis indicated a downregulation of MEP4 and SUB1 gene expression in response to EA and SK treatment.
Conclusions:
- EA and SK exhibit antifungal activity against *T. rubrum* by disrupting the fungal cell membrane.
- The mechanism involves the inhibition of ergosterol biosynthesis, specifically C14 demethylase and squalene epoxidase activity, through the downregulation of MEP4 and SUB1.
- EA and SK represent potential natural antifungal agents for future clinical applications.
