Vanillin Enhances Photobiomodulation Wound Healing by Modulating Glyco‐Oxidative Stress and Glucose Dysmetabolism in Diabetic Wounded Fibroblast Cells

Delayed wound healing is among the major peripheral complications of diabetes. Synergistic treatment of diabetic wounds (DW) with phytochemicals and non-invasive techniques has shown promising results. The synergistic effect of vanillin and photobiomodulation (PBM) on DW healing, and their modulatory effect on oxidative stress and glucose metabolism was investigated in DW fibroblast cells (WS1). DW cells were treated with vanillin and vanillin + PBM. Control consisted of WS1 cells, untreated DW cells, and DW cells treated with PBM. Diabetes was induced by repeated growth in complete MEM containing high D-glucose (22.6 mM/L). Wounds were induced by central scratching. Cells were treated with vanillin at various concentrations for 2 h prior to PBM at 660 nm with a fluence of 5 J/cm² for an irradiation time of 780 s, followed by 24 h incubation. Induction of DW led to a decreased glutathione level, and decreased superoxide dismutase, catalase, glutathione reductase, glyoxalase, and Na/K-ATPase activities, while concomitantly increasing the activities of fructose-1,6-bisphosphatase, glucose 6-phosphatase, E-NTPDase, and 5-lipoxygenase. These levels and activities were reversed following treatment with 12 μg/mL vanillin, and 6 μg/mL vanillin + PBM having the best effects. However, treatment with 24 μg/mL vanillin and vanillin + PBM showed no significant effects. Except for cells treated with 24 μg/mL vanillin and vanillin + PBM, morphological analysis indicated wound closures compared to the controls. These results indicate the synergistic therapeutic effect of vanillin + PBM on the management of diabetic wounds, with 6 μg/mL vanillin + PBM displaying the best effect.