Diabetic
ulcer is usually seen in people with uncontrolled
blood sugar. Reportedly, many factors such as impaired
glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic
ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of
paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic
ulcer was established. High
glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without
paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and
collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and
vascular endothelial growth factor (
VEGF). Western blot was used to detect
interleukin (IL)-1β,
tumor necrosis factor (TNF)-α,
IL-4,
IL-10, CD31, VEGFA, and
collagen I/III. The expression of iNOS and
arginase 1 was revealed by immunofluorescence staining.
Paeonol treatment augmented
collagen deposition and the expression of Ki67, CD31,
VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced
wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro,
paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high
glucose.
Paeonol accelerates the healing of diabetic
ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.