Comparative Effects of Topically Applied Tocotrienol (T3) Isomers in Promoting Cutaneous Wound Healing in Obese Type 2 Diabetes Mice

Diabetic foot ulcers are a significant complication, especially for type 2 diabetes and obese patients. This is mainly caused by an excessive and persistent inflammatory-oxidative stress environment in the wounds, which impedes healing. Tocotrienol, a phytochemical with antioxidant and anti-inflammatory properties, holds notable therapeutic potential. Therefore, this study aimed to investigate the healing effects of topically applied tocotrienol isomers (α-, β-, δ- and γ-T3) on full-thickness excisional cutaneous wounds in male B6.V-Lepob/JRj mice. Treatment effects were evaluated through wound closure rate, histopathology, collagen deposition, hydroxyproline content and the levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione, malondialdehyde and myeloperoxidase in the wound granulation tissues. Cytokine, chemokine, and growth factor levels were quantified using the Luminex assay. The presence of isomers in wound granulation tissue was determined by high-performance liquid chromatography. Results showed that T3 isomers facilitated tissue regeneration and hastened wound closure. They significantly reduced oxidative stress by lowering malondialdehyde and myeloperoxidase levels and by enhancing antioxidant activity and production. These isomers effectively diminished pro-inflammatory cytokines and chemokines, while increasing anti-inflammatory cytokines and modulating growth factors, thereby promoting wound healing in B6.V-Lepob/JRj mice. These findings suggest that T3 isomers may serve as therapeutic agents that enhance cutaneous wound healing in individuals with diabetes.