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Original Article

Korean J Physiol Pharmacol 2023; 27(5): 437-448

Published online September 1, 2023

Copyright © Korean J Physiol Pharmacol.

Paeonol accelerates skin wound healing by regulating macrophage polarization and inflammation in diabetic rats

Zuyang Zhang#, Tianhua Chen#, Wei Liu, Jiepeng Xiong, Liangdong Jiang*, and Mingjiang Liu*

Department of Orthopedics, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan 410004, China

Correspondence to:Mingjiang Liu
Liangdong Jiang

#These authors contributed equally to this work as co-first authors.

Author contributions: Z.Z., T.C., and W.L. conceived the ideas; designed the experiments. Z.Z., T.C., W.L., and J.X. performed the experiments. W.L. and J.X. analyzed the data. Z.Z. and T.C. provided critical materials. Z.Z., T.C., W.L., and J.X. wrote the manuscript. M.L. and L.J. supervised the study. All the authors have read and approved the final version for publication.

Received: December 24, 2022; Revised: April 28, 2023; Accepted: June 2, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.

Keywords: Diabetes, Macrophage polarization, Paeonol, Wound healing