Li Kun, Zhang Yingying, Diao Yunpeng, Fan Shuyuan
College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China.
College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China.
Int Immunopharmacol. 2025 Apr 4;151:114347. doi: 10.1016/j.intimp.2025.114347. Epub 2025 Feb 22.
Diabetic foot ulcers are a common complication in people with diabetes, and patients with severe disease are at risk of amputation. Current studies have found that one of the reasons for the difficulty in healing diabetic foot ulcers is the Abnormal polarization of the M1/M2 phenotype of macrophages, which leads to a prolonged inflammatory period of the wound. The aim of this study was to investigate whether paeonol can promote the polarization of macrophages towards the M2 type and whether M2 type macrophages can regulate the DDIT4-mTOR signaling pathway and slow down the inflammatory response of diabetic foot ulcers.
C57BL/6 mice were used to establish an animal model of diabetic foot ulcers and the effect of paeonol on wound healing was investigated. The effects of paeonol on wound healing of foot ulcer in diabetic mice were evaluated using histological staining and immunohistochemistry. The molecular mechanism of refractory healing of foot ulcers was speculated through network pharmacology. The effects of Paeonol on phenotypic polarization of macrophages and the mechanism of inhibiting inflammation were studied by q-PCR, ELISA, immunofluorescence and Western.
Paeonol can effectively promote wound healing in diabetic mice. HE staining showed that paeonol could improve the inflammatory infiltration in the ulcer wound of diabetic mice; Masson trichromatic staining showed that paeonol could increase the increase of muscle fibers and collagen in the wound tissue of diabetic mice; immunofluorescence results showed that paeonol could increase the angiogenesis in the wound tissue of diabetic mice. Network pharmacological analysis showed that the molecular mechanism of paeonol in treating diabetic wound healing may be through DDIT4-mTOR signaling pathway. q-PCR, ELISA, immunofluorescence and Western blot showed that paeonol could reduce the expression of the signature protein CD86 and inflammatory factors in M1 macrophages, and promote the phenotypic polarization of M2 macrophages, which is the mechanism of inhibiting inflammation by activating DDIT4-mTOR signaling pathway.
Paeonol can promote the polarization of macrophages towards M2 type, reduce inflammatory response and accelerate wound surface healing through DDIT4-mTOR signaling pathway, providing a new therapeutic strategy for the treatment of diabetic foot ulcers.
糖尿病足溃疡是糖尿病患者常见的并发症，重症患者有截肢风险。目前研究发现，糖尿病足溃疡难以愈合的原因之一是巨噬细胞M1/M2表型极化异常，导致伤口炎症期延长。本研究旨在探讨丹皮酚是否能促进巨噬细胞向M2型极化，以及M2型巨噬细胞是否能调节DDIT4-mTOR信号通路并减缓糖尿病足溃疡的炎症反应。
采用C57BL/6小鼠建立糖尿病足溃疡动物模型，研究丹皮酚对伤口愈合的影响。采用组织学染色和免疫组化方法评价丹皮酚对糖尿病小鼠足部溃疡伤口愈合的作用。通过网络药理学推测足部溃疡难愈合的分子机制。采用q-PCR、ELISA、免疫荧光和Western印迹法研究丹皮酚对巨噬细胞表型极化及抑制炎症的机制。
丹皮酚能有效促进糖尿病小鼠伤口愈合。HE染色显示，丹皮酚可改善糖尿病小鼠溃疡伤口的炎症浸润；Masson三色染色显示，丹皮酚可增加糖尿病小鼠伤口组织中肌纤维和胶原蛋白的增加；免疫荧光结果显示，丹皮酚可增加糖尿病小鼠伤口组织中的血管生成。网络药理学分析表明，丹皮酚治疗糖尿病伤口愈合的分子机制可能是通过DDIT4-mTOR信号通路。q-PCR、ELISA、免疫荧光和Western印迹显示，丹皮酚可降低M1巨噬细胞中标志性蛋白CD86和炎症因子的表达，促进M2巨噬细胞的表型极化，这是通过激活DDIT4-mTOR信号通路抑制炎症的机制。
丹皮酚可促进巨噬细胞向M2型极化，减轻炎症反应，通过DDIT4-mTOR信号通路加速创面愈合，为糖尿病足溃疡的治疗提供了新的治疗策略。
