One of the major reasons for the delayed wound healing in diabetes is the dysfunction of endothelial progenitor cells (EPCs) induced by hyperglycaemia. Improvement of EPC function may be a potential strategy for accelerating wound healing in diabetes. Procyanidin B2 (PCB2) is one of the major components of procyanidins, which exhibits a variety of potent pharmacological activities. However, the effects of PCB2 on EPC function and diabetic wound repair remain elusive. We evaluated the protective effects of PCB2 in EPCs with high glucose (HG) treatment and in a diabetic wound healing model. EPCs derived from human umbilical cord blood were treated with HG. The results showed that PCB2 significantly preserved the angiogenic function, survival and migration abilities of EPCs with HG treatment, and attenuated HG‐induced oxidative stress of EPCs by scavenging excessive reactive oxygen species (ROS). A mechanistic study found the protective role of PCB2 is dependent on activating nuclear factor erythroid 2‐related factor 2 (Nrf2). PCB2 increased the expression of Nrf2 and its downstream antioxidant genes to attenuate the oxidative stress induced by HG in EPCs, which were abolished by knockdown of Nrf2 expression. An in vivo study showed that intraperitoneal administration of PCB2 promoted wound healing and angiogenesis in diabetic mice, which was accompanied by a significant reduction in ROS level and an increase in circulating EPC number. Taken together, our results indicate that PCB2 treatment accelerates wound healing and increases angiogenesis in diabetic mice, which may be mediated by improving the mobilization and function of EPCs.

中文翻译：

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原花青素 B2 通过激活 Nrf2 改善糖尿病小鼠内皮祖细胞功能并促进伤口愈合

糖尿病伤口愈合延迟的主要原因之一是高血糖引起的内皮祖细胞（EPC）功能障碍。改善 EPC 功能可能是加速糖尿病伤口愈合的潜在策略。原花青素 B2 (PCB2) 是原花青素的主要成分之一，具有多种强效药理活性。然而，PCB2 对 EPC 功能和糖尿病伤口修复的影响仍然难以捉摸。我们评估了 PCB2 在高糖 (HG) 治疗和糖尿病伤口愈合模型中的 EPC 中的保护作用。来源于人脐带血的 EPCs 用 HG 处理。结果表明，PCB2 显着保留了 HG 处理的 EPCs 的血管生成功能、存活和迁移能力，并通过清除过量的活性氧 (ROS) 来减弱 HG 诱导的 EPCs 氧化应激。一项机制研究发现，PCB2 的保护作用取决于激活核因子红细胞 2 相关因子 2 (Nrf2)。PCB2 增加了 Nrf2 及其下游抗氧化基因的表达，以减弱 HG 在 EPCs 中诱导的氧化应激，通过敲低 Nrf2 表达消除了这种氧化应激。一项体内研究表明，腹腔内给予 PCB2 可促进糖尿病小鼠的伤口愈合和血管生成，同时伴随着 ROS 水平的显着降低和循环 EPC 数量的增加。总之，我们的结果表明，PCB2 治疗可加速糖尿病小鼠的伤口愈合并增加血管生成，这可能是通过改善 EPC 的动员和功能来介导的。