Topical eucalyptol accelerates the healing of MRSA-infected diabetic wounds in rats by regulating TLR4, NF-κB, VEGFA and MMP-9 pathways

Diabetic-infected wounds are complex conditions that cause chronic inflammation that is difficult to heal. Although eucalyptol (1.8 cineole) has been shown to have antimicrobial, antioxidative and anti-inflammatory properties, its effectiveness in diabetic-infected wounds has not yet been proven.

In this study, 35 male Wistar albino rats were induced with streptozotocin and inoculated with methicillin-resistant Staphylococcus aureus (MRSA) after full-thickness skin wounds were inoculated. The animals were randomly assigned into five groups: Control (C), Vehicle (V), 2% Mupirocin (M), 5% topical eucalyptol (E5), and 10% topical eucalyptol (E10). Treatments were applied twice daily for 21 days (n = 7 per group). Wound areas, quantitative tissue cultures (CFU/g), oxidative stress parameters malondialdehyde (MDA), glutathione (GSH), catalase (CAT), glutathione peroxidase-1 (GPx1) histopathological and immunohistochemical changes (edema, inflammatory infiltration, angiogenesis, re-epithelialization, granulation/vascular endothelial growth factor A (VEGFA), matrix metalloproteinase-9 (MMP-9), nuclear factor kappa B (NF-κB), and toll-like receptor 4 (TLR4) were examined.

The current results showed that MDA levels decreased and GSH, CAT and GPx1 levels increased in the E5 and E10 groups compared to the control group. On the other hand, histopathologically, it was determined that edema and inflammatory infiltration decreased and angiogenesis, reepithelialization and granulation tissue formation processes increased in the E5 and E10 groups compared to the control group. Additionally, immunohistochemical findings revealed that E5 and E10 groups caused downregulation of TLR4, NF-κB and MMP-9 protein expressions and upregulation of VEGFA protein expression.

Taken together, the present results have been shown that topical eucalyptol application reduces the bacterial load in MRSA-infected diabetic wounds, alleviates oxidative stress and inflammation at the cellular level, and promotes angiogenesis and extracellular matrix remodeling, thus promoting faster and more regular wound healing.