Abstract
Background
A wound is an impairment of the structural and functional integrity of the skin. Diabetes mellitus (DM) is associated with several complications, including diabetic wounds (DWs), which are among the most frequent and devastating. Delayed healing in diabetes is associated with inflammation, oxidative stress, impaired tissue regeneration, and increased susceptibility to infection. Citronellol, a natural monoterpenoid alcohol, possesses anti-inflammatory, antioxidant, and antimicrobial properties that may enhance wound healing by reducing oxidative stress and infection and promoting tissue repair and collagen deposition.
Aim
To investigate the potential of citronellol to enhance wound healing by modulating inflammatory responses, reducing oxidative stress, and promoting tissue regeneration, particularly in diabetic mice.
Methods
Diabetes will be induced in mice by intraperitoneal injection of streptozotocin (STZ). A dorsal full-thickness excisional wound will be created using a 6-mm biopsy punch under ketamine/xylazine anesthesia. One hundred forty-four male Swiss albino mice (25–35 g, 8–12 weeks old) will be randomly allocated into eight groups (n=18/group). Non-diabetic groups will include: AI, negative control receiving gel base only; AII, wounded mice receiving gel base; AIII, wounded mice receiving silver sulfadiazine; and AIV, wounded mice receiving citronellol 5% (w/w) gel. Diabetic groups will include corresponding groups BI–BIV. Treatments will be applied topically once daily for 14 consecutive days.
Outcome Measurements
Standardized wound photographs with a scale marker will be obtained on days 0, 3, 7, 10, 12, and 14. Wound area and percentage closure will be determined using ImageJ. Histological healing will be evaluated using a modified HEALS-A scale, assessing epithelialization, angiogenesis, leukocyte infiltration, and skin appendage regeneration, while clinical healing will be assessed using the GRADES scale on days 7 and 14. Serum and tissue samples collected on day 3 will be analyzed by ELISA for IL-10, TNF-α, and IL-2. Western blot analysis on days 7 and 14 will assess SMAD2, VEGF, α-SMA, and TGF-β1 expression and activation. Hydroxyproline content will be measured colorimetrically as an indicator of collagen deposition.
