Therapeutic Potential of Passiflora edulis Sims Seed Extract on Molecular and Histological Markers of Wound Healing in a Diabetic Rat Model

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia and oxidative stress, which contribute to vascular dysfunction, tissue damage, hypoxia, and an increased risk of foot ulceration and amputation. Uncontrolled hyperglycemia elevates reactive oxygen species (ROS), increases malondialdehyde (MDA) production, and activates the NF-κB signaling pathway, leading to the release of pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6. This cascade promotes caspase-3 activation and inflammatory cell damage in keratinocytes and fibroblasts, impairing extracellular matrix formation and re-epithelialization. Although antioxidant defenses play a critical role in wound healing, scientific validation of natural topical agents remains limited. Seeds of Passiflora edulis Sims, rich in flavonoids, gallic acid derivatives, and antioxidant compounds with anti-inflammatory and antimicrobial properties, have been identified as promising candidates for wound therapy. This study investigated molecular pathways involving epidermal growth factor (EGF), MDA, TNF-α, collagen deposition, and epithelialization as key regulators of oxidative stress, inflammation, and tissue repair. A post-test-only experimental design was conducted using 25 male Wistar rats with streptozotocin-nicotinamide-induced diabetes, divided into 5 groups: Negative control (ointment base), positive control (Tribee salf), and 3 treatment groups receiving Passiflora edulis seed extract (PFSE) at doses of 50, 100, and 150 mg/g. Molecular markers were analyzed using ELISA (MDA, EGF, caspase-3), immunohistochemistry (TNF-α), and histological staining (Masson’s Trichrome for collagen and hematoxylin-eosin for epithelialization). Data were statistically evaluated using ANOVA with Bonferroni post hoc, independent t-tests, and Kruskal-Wallis tests, with significance set at p < 0.05. The results demonstrated that PFSE significantly reduced MDA, TNF-α, and caspase-3 levels, while increasing EGF expression, collagen deposition, and epithelialization compared with the control groups (p < 0.05). These findings highlight the therapeutic potential of Passiflora edulis seed extract as an antioxidant, anti-inflammatory, and wound-healing agent for diabetic wounds. HIGHLIGHTS Experimental Model 25 male Wistar rats, adapted for 7 days. 5 groups: Negative control (ointment base), positive control (Tribee salf), and 3 treatment groups with Passiflora edulis Sims seed extract (PFSE 50, 100 and 150 mg/g). Diabetes was induced using streptozotocin (45 mg/kg, i.p.) combined with nicotinamide (110 mg/kg, i.p.). Wounds were created by punch biopsy followed by MRSA inoculation (10⁶ CFU). Treatment: Topical application of PFSE according to dosage. Assessment Parameters Biomarkers: MDA, Caspase-3, and EGF (ELISA); TNF-α (immunohistochemistry). Histology: Collagen (Masson’s Trichrome) and epithelialization (H&E). Key findings: PFSE accelerated wound healing in diabetic rats infected with MRSA by modulating oxidative stress, inflammation, apoptosis, and tissue repair biomarkers. GRAPHICAL ABSTRACT