Polyphenol-rich Cistus salviifolius L. extract exerts fungicidal activity against dermatophytes through severe ultrastructural disruption

ETHNOPHARMACOLOGICAL RELEVANCE: Cistus salviifolius L. (Cistaceae) has long been employed in Mediterranean traditional medicine for the topical treatment of skin disorders, including infections, wounds, and inflammatory conditions. Despite its recognized ethnobotanical relevance, its antidermatophytic potential remains insufficiently characterized. AIM OF THE STUDY: This study aimed to pharmacologically validate the traditional use of C. salviifolius against cutaneous fungal infections by evaluating the antifungal activity of a polyphenol-rich extract against dermatophytes, investigating its mechanism of action, and assessing its skin-protective properties in a reconstructed human epidermis (RHE) model. MATERIALS AND METHODS: Antifungal activity was determined by broth microdilution assays following EUCAST guidelines to establish minimum inhibitory and fungicidal concentrations. Ultrastructural alterations were examined by transmission electron microscopy (TEM). The extract was further evaluated in dermatophyte-infected RHE through fungal DNA quantification, transepithelial electrical resistance measurements, histological analysis, and cytokine release assays. Antioxidant activity and inhibition of extracellular matrix-degrading enzymes were also assessed. RESULTS: The extract showed selective fungicidal activity against dermatophytes, with MIC values of 78 mg/L against Trichophyton rubrum and Microsporum canis. TEM revealed severe cellular damage, including extensive vacuolization, membrane detachment, and cytoplasmic disorganization. In the RHE model, topical treatment reduced fungal burden, preserved epidermal barrier integrity, and attenuated IL-1α and IL-8 release, particularly against T. rubrum. Additionally, the extract displayed strong antioxidant activity and significantly inhibited collagenase, elastase, and hyaluronidase. CONCLUSIONS: These findings provide pharmacological support for the traditional use of C. salviifolius in skin infections and identify this polyphenol-rich extract as a promising multifunctional candidate for topical dermatophytosis management.