As one of the most frequent diabetic complications, diabetic foot ulcer (DFU) can cause limb ischemia or even amputation. Paeoniflorin (PF) has been reported to possess many kinds of biological functions, such as antioxidant and anti-inflammatory effects. However, the role of PF in DFU remains unknown. In this study, streptozotocin (STZ)-induced diabetic rat models and high glucose (HG)-treated Human immortalized keratinocytes (HaCaT) cells were established. Histological analysis, immunohistochemistry, Electrophoretic mobility shift assay, MTT assay, TUNEL assay, oxidative stress analysis, ELISA assay and western blot were used to investigate the role and underlying mechanisms of PF on healing in DFU. Our results showed that the STZ-induced diabetic rats had delayed wound healing compared with the normal rats, exhibited by intense oxidative DNA damage, low vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1) expression, as well as increased apoptosis. PF treatment activated the expression of nuclear factor-E2-related factor 2 (Nrf2) and improved wound healing in DFU rats. Our in vitro experiments confirmed that PF accelerated wound healing through the Nrf2 pathway under hyperglycemic conditions, with alleviated oxidative stress, increased cell proliferation and migration, decreased apoptosis, and increased the expression of VEGF and TGF-β1. Our study demonstrates the therapeutic benefits of PF in diabetic wound healing, which provides a reference for future clinical trials using PF in DFU treatment.

作为糖尿病最常见的并发症之一，糖尿病足溃疡（DFU）可导致肢体缺血甚至截肢。据报道，芍药苷（PF）具有多种生物学功能，如抗氧化和抗炎作用。然而，PF 在 DFU 中的作用仍然未知。在这项研究中，建立了链脲佐菌素 (STZ) 诱导的糖尿病大鼠模型和高糖 (HG) 处理的人永生化角质形成细胞 (HaCaT) 细胞。组织学分析、免疫组织化学、电泳迁移率变化测定、MTT 测定、TUNEL 测定、氧化应激分析、ELISA 测定和蛋白质印迹用于研究 PF 在 DFU 愈合中的作用和潜在机制。我们的结果表明，与正常大鼠相比，STZ 诱导的糖尿病大鼠的伤口愈合延迟，表现为强烈的氧化性 DNA 损伤、低血管内皮生长因子 (VEGF) 和转化生长因子 β1 (TGF-β1) 表达以及细胞凋亡增加。PF 治疗激活了核因子-E2 相关因子 2 (Nrf2) 的表达并改善了 DFU 大鼠的伤口愈合。我们的体外实验证实PF在高血糖条件下通过Nrf2通路加速伤口愈合，减轻氧化应激，增加细胞增殖和迁移，减少细胞凋亡，并增加VEGF和TGF-β1的表达。我们的研究证明了 PF 在糖尿病伤口愈合中的治疗益处，这为未来使用 PF 治疗 DFU 的临床试验提供了参考。