Background/Objectives: Diabetic foot ulcers infected with methicillin-resistant Staphylococcus aureus (MRSA) heal poorly and respond inadequately to conventional antibiotic therapy. This study developed a Micromeria fruticosa essential oil-loaded nanoemulsion (Mf-NE) as a topical treatment for such wounds. Methods: The essential oil was obtained by hydrodistillation and analyzed by GC–MS. Nanoemulsions were developed from pseudoternary phase diagrams using oleic acid and a Cremophor^® EL/Tween 80–Transcutol^® system (2:1 surfactant/cosurfactant) and characterized physicochemically. Antibacterial activity against MRSA (ATCC 43300) was assessed by agar well diffusion and microdilution, antioxidant activity by DPPH and ABTS assays, and cytocompatibility by MTT assay on L929 fibroblasts. Efficacy was evaluated over 12 days in a streptozotocin-induced MRSA-infected diabetic wound model in rats. Results: Pulegone (42.81%) and piperitenone (29.73%) were the major constituents. Incorporation of 5% (w/w) essential oil raised the droplet size from 214.5 ± 14.4 to 292.9 ± 9.9 nm; both formulations had a dermatologically acceptable pH and Newtonian flow behavior. Mf-NE produced a 16.1 mm inhibition zone and a MIC of 1.25 mg/mL, whereas NE produced no inhibition zone and had a MIC of 5 mg/mL. Radical scavenging reached 61.5% by DPPH at 10 mg/mL and 71.5% by ABTS at 0.2 mg/mL, and cell viability remained above 87%. The NE and Mf-NE formulations also demonstrated good biocompatibility in L929 fibroblast cells. Topical Mf-NE reduced the remaining wound area to 4.8 ± 0.9% of the initial area by day 12, compared with 21.0 ± 1.9% for Fucidin, 26.1 ± 1.9% for NE and 57.2 ± 1.3% for the untreated group; bacterial colonization was almost completely suppressed, TNF-α and IL-1β expression was significantly decreased, and composite histopathological scores were lower than in the untreated group (p = 0.0007). Conclusions: Mf-NE is a promising topical candidate for MRSA-infected diabetic wounds. Formulation-specific dermal and systemic safety requires further evaluation.

Gentamicin is an aminoglycoside antibiotic and has therapeutic importance in the treatment of Gram-negative aerobic bacterial infections. However, its clinical use is limited by nephrotoxicity, in which oxidative stress plays an important role. In this study, we investigated the protective effects of Cyclotrichium niveum, an endemic plant with antioxidant properties, against gentamicin-induced nephrotoxicity in rats. Renal injury and protection were assessed using blood urea nitrogen (BUN) and serum creatinine as markers of renal function, malondialdehyde (MDA) as a marker of oxidative stress, and histopathological evaluation of renal cortical injury. We first characterized the chemical composition of C. niveum essential oil (EO) by GC-MS, identifying pulegone as its major constituent (79.6%). Next, we evaluated the in vitro antioxidant activity of EO and isolated pulegone using the DPPH assay. Their protective effects were then examined in vivo at two dose levels each (EO, 200 and 400 mg/kg/day; pulegone, 50 and 100 mg/kg/day, p.o.) in rats receiving gentamicin (100 mg/kg/day, i.m.) for 8 days. Both EO and pulegone exhibited DPPH radical-scavenging activity. Gentamicin induced pronounced renal injury, whereas co-administration of either EO or pulegone provided protection, with more pronounced effects at the higher doses. In particular, gentamicin increased BUN and creatinine 2.74- and 2.37-fold, respectively (p < 0.001 for both), and produced grade 4–5 cortical injury in all histologically evaluated animals. At the higher doses, EO and pulegone reduced BUN by 56% and 64%, respectively (p = 0.042 and p < 0.001), and MDA by 57% and 55%, respectively (p = 0.006 for both). Pulegone additionally reduced creatinine by 39% (p = 0.041). Both treatments significantly improved histopathological injury grade (p = 0.002 and p = 0.008 for EO and pulegone, respectively). Together, these findings demonstrate that C. niveum EO and pulegone attenuate gentamicin-induced renal injury across functional, oxidative, and structural measures, with the strongest protection observed at the higher doses. Their in vitro antioxidant activity and attenuation of lipid peroxidation in vivo support an antioxidant contribution to the nephroprotective response, while the activity of isolated pulegone identifies it as an important bioactive contributor to the protective effects of C. niveum EO.