Diabetes mellitus (DM) is a metabolic disease that delays the healing process, including the interruption of the processes of angiogenesis and vasculogenesis. The etiology of most angiogenic-related diseases, such as diabetes complications, includes the presence of hypoxia caused by declined vascular endothelium growth factor (VEGF) and CD-31. d-limonene, one of the main constituents of Citrus limon, is considered to have angiogenic, antioxidant, hypoglycemic, and anti-inflammatory activities. However, the exact mechanism of this process remains unclear. This study aimed to determine the potential of C. limon as a medication for diabetic ulceration. A total of 30 Wistar rats (Rattus novergicus) induced with DM and traumatic ulcers on the lower lip mucosa were divided into six groups-three each for control and treatment groups. Control groups were treated with CMC 5% gel, and treatment groups were administered with C. limon peel essential oil gel. The expression of VEGF and CD-31 was observed on days 5, 7, and 9. Immunohistochemical examinations were performed with the monoclonal antibodies anti-VEGF and anti-CD-31. ANOVA was conducted to analyze the differences between the groups (p<0.05). An increase in VEGF and CD-31 expression in the treatment group was observed compared with that of the control group (p<0.05). Citrus limon peel essential oil gel increased VEGF and CD-31 expression during the healing process of traumatic ulcers in diabetes-afflicted Wistar rats.
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