<b>Superior efficacy of 2% <i>Olea europaea</i> leaf extract ointment compared with Fucidin^® in accelerating wound closure and resolving infection in rat models</b>

Background: Impaired wound healing, intensified by microbial infection and increasing antibiotic resistance, underscores the urgent need for novel therapeutic agents. Olea europaea L. (olive) leaf, which is rich in bioactive polyphenols, is a promising candidate for its traditional medicinal use. Aim: This study aimed to evaluate the wound-healing efficacy of a topical O. europaea leaf extract (OLE) ointment in clean and infected wound models by directly comparing its performance with that of a standard topical antibiotic. Methods: The phytochemical characterization and in vitro antibacterial activity of 75% ethanolic OLE were assessed. Ointments containing 1% and 2% (w/w) OLE were developed and characterized physicochemically. Their efficacy was evaluated in vivo using full-thickness excisional wounds in rats and compared with untreated, vehicle, and Fucidin®-treated controls. Wound models infected with Staphylococcus aureus and Pseudomonas aeruginosa were also established. Wound closure was monitored planimetrically for 21 days. Results: OLE was rich in phenols, flavonoids, and tannins and exhibited potent in vitro antibacterial activity against both pathogens, showing superior inhibition of S. aureus compared with that of Fucidin®. In the clean-wound model, 2% OLE ointment induced the most rapid healing, achieving complete closure by day 13, significantly outperforming Fucidin® (day 18; p < 0.01). In the infected models, both OLE ointments significantly accelerated healing and infection resolution compared with the controls. Notably, the 1% OLE formulation demonstrated superior early activity in infected wounds, reaching 100% closure by days 12 (S. aureus) and 13 (Ps. aeruginosa), while outperforming Fucidin® (days 18–20). Conclusion: The 2% O. europaea leaf extract ointment possesses potent dose-dependent wound-healing and broad-spectrum antimicrobial activities, outperforming a standard antibiotic in clean wounds and showing high efficacy in infected models. Its multi-target action, derived from a complex phytochemical profile, validates its traditional use and highlights its potential as a leading natural formulation for advanced wound management, particularly in the era of antimicrobial resistance.