Mastoparan, a Wasp Venom–Derived Peptide, Promotes Healing in <i>Candida albicans</i> –Infected Wounds through Antifungal and Anti-Inflammatory Mechanisms

BackgroundCandida albicans–infected wounds are difficult to treat due to delayed healing, excessive inflammation, and oxidative stress. Mastoparan, a bioactive peptide with antimicrobial and immunomodulatory properties, was investigated for its potential to enhance wound healing and antifungal activity. This study evaluated its effects on oxidative stress, inflammation, and the expression of TGF-β1, VEGF, NF-κB, and COL1A1 in a C. albicans–infected wound model, compared with ketoconazole.Materials and methodsThe antifungal activity of mastoparan was assessed in vitro using inhibition zone analysis and MIC determination against C. albicans. For comparison, ketoconazole was tested at 10 µg/mL in vitro and as a 2% topical formulation in vivo. In vivo wound healing was evaluated using two MIC-informed doses of mastoparan (7.8 and 15.6 mg/kg/day) administered topically once daily in non-infected and infected rat wound models, in comparison with ketoconazole. Eight groups were studied (n = 12/group): untreated control, wounded untreated, wounded + mastoparan (two doses), infected untreated, infected + mastoparan (two doses), and infected + ketoconazole (reference). Treatments were applied for 14 days. Wound healing, histology, ultrastructure, oxidative stress, inflammation, and gene expression analyzed.ResultsMastoparan showed strong antifungal activity and dose-dependently enhanced infected wound healing by accelerating wound closure, reducing fungal burden, improving tissue integrity, decreasing oxidative stress and inflammation, and promoting wound-healing–related gene expression, with the greatest effects observed at 15.6 mg/kg/day.ConclusionsMastoparan exerts potent antifungal activity and accelerates wound healing through coordinated antioxidant, anti-inflammatory, and pro-regenerative mechanisms, supporting its potential as a therapeutic alternative to conventional antifungal agents.