Objective: 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. Methods: 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). Result: An increase in VEGF and CD-31 expression in the treatment group was observed compared with that of the control group (p < 0.05). Conclusion: Citrus limon peel essential oil gel increased VEGF and CD-31 expression during the healing process of traumatic ulcers in diabetes-afflicted Wistar rats.

Original languageEnglish
Pages (from-to)380-385
Number of pages6
JournalJournal of Oral Biology and Craniofacial Research
Issue number3
Publication statusPublished - 1 May 2023


  • Agricultural innovation
  • CD-31
  • Citrus limon
  • Diabetic ulceration
  • Human health
  • VEGF


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