Numerous medicinal plants are reported to have activity against dermatophytes, however, there are limited studies providing insights into their mechanism of action, which may be hindering their clinical use. This study aimed to investigate the antifungal activity and toxicity of three South African plants traditionally used to treat skin infections caused by dermatophytes and to investigate the mechanism of action of the most active plant extract. Searsia lancea showed the highest antifungal activity against Microsporum canis (MIC 0.156 mg/mL). Warburgia salutaris and M. comosus showed no toxic effects on HaCaT cells while S. lancea exhibited moderate cytotoxicity. The most active combination of S. lancea combined with M. comosus showed to be non-toxic. Searsia lancea and M. comosus were non-mutagenic at 500 μg/mL. The ethyl acetate partition of S. lancea demonstrated a two-fold increase in activity against Microsporum species while fraction fifteen (F15) exhibited a four-fold increase in activity against T. mentagrophytes. Two compounds in F15 were identified as sakuranetin and gentisic acid, with sakuranetin showing the best activity against T. mentagrophytes. Electron microscopy showed alterations of hyphal surfaces in the form of shrinkage and folding of the plasma membrane (24-48 h) and breakage and leakage of cytoplasmic material (72 h). The RT-qPCR showed significant repression (p < 0.01) of the SSU1 gene of M. canis treated with S. lancea (0.312 mg/mL) after 2 and 7 days. The findings not only support traditional usage of S. lancea but also provide targets of S. lancea's anti-dermatophytic activity.
Keywords: Antifungal; Chromatography; Dermatophytes; Microscopy; RT-qPCR; Searsia lancea; Toxicity.
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