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Introduction: Cutaneous wound healing is regulated by cellular and molecular mechanisms that can be impaired in diabetes mellitus, increasing the risk of amputation. The high cost and possible adverse effects of synthetic therapies motivate the search for natural compounds. The hydroalcoholic extract of Euterpe oleracea Mart. seed (ASE) has shown anti-inflammatory effects, suggesting potential in wound healing. Objective: To evaluate ASE effects on cutaneous wound repair in male Wistar rats with type 1 diabetes mellitus. Materials and Methods: Sixty male Wistar rats (3 months old) were divided into four groups: control (CT), control treated with ASE (CTA, 200 mg/kg/day, gavage), diabetic (DM), and diabetic treated with ASE (DMA). Diabetes was induced in DM and DMA by streptozotocin (STZ, 50 mg/kg, i.p.). A 4 cm² wound was made on the dorsum, and CTA and DMA received ASE until day 14. Lesions were processed for histology or lysed in RIPA buffer. Data were analyzed by two-way ANOVA and Bonferroni's post-test. Results: DM and DMA showed higher fasting glucose from 72 h after STZ (p<0.0001) and lower insulin than healthy animals (CT vs. DM, p=0.0085; CTA vs. DMA, p=0.0020). DM showed a higher wound area and lower macroscopic re-epithelialized area than CT (p=0.0493 and p=0.0003), while treatment increased macroscopic re-epithelialization in DMA vs. DM (p=0.0030). No difference was found in collagen I immunolabeling; however, DM showed higher percentage of collagen III than CT (p=0.0017), which was reduced in DMA vs. DM (p=0.0161). CD68 immunolabeling was higher in DM vs. CT (p=0.0454), with no treatment effect in DMA. Tissue IL-6 and IL-1β were higher in DM vs. CT (p=0.0011, p<0.0001) and reduced in DMA vs. DM (p=0.0374, p=0.0046). Conclusions: ASE promoted macroscopic re-epithelialization, modulated collagen deposition, and reduced inflammatory cytokines, suggesting benefit for tissue repair in diabetic animals, despite persistent systemic metabolic alterations.
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