Tang Guangjun, Wang Ying, Deng Pin, Wu Junde, Lu Zhongwen, Zhu Ruizheng, Guo Hui, Zhang Yunhui, Mo Xingjie, Chen Zhaojun
Beijing University of Chinese Medicine, Beijing, China.
Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China.
Sci Rep. 2025 Apr 11;15(1):12492. doi: 10.1038/s41598-025-97831-5.
Delayed wound healing in diabetic foot ulcer (DFU) is a major cause of amputations, with ferroptosis impeding recovery. Dracorhodin (DP), a flavonoid from Dragon's Blood, has shown anti-inflammatory and wound-healing properties, though its molecular mechanisms is unclear. This study investigates DP's role in DFU treatment through bioinformatics and experimental approaches. A rat model of DFU was created with a high-fat/high-glucose diet and streptozotocin (STZ) induction, and wound healing was monitored after applying varying DP doses. Histopathological analysis and ELISA assessed tissue changes, inflammatory markers, and growth factors. Network pharmacology and molecular docking were used to identify core targets and pathways, while human umbilical vein endothelial cells (HUVECs) were used for in vitro testing. The results demonstrated that DP accelerated wound healing in DFU rats in a dose-dependent manner by enhancing collagen synthesis, angiogenesis, and growth factor levels, while simultaneously reducing inflammation and ROS levels. Network pharmacology and molecular docking analyses identified the Nrf2-mediated ferroptosis pathway as a potential key mechanism underlying DP's therapeutic effects in DFU. In vitro experiments further revealed that DP improved cell viability and migration, while decreasing ROS and lipid peroxidation levels, effects attributed to Nrf2 pathway activation. These outcomes were significantly attenuated by the Nrf2 inhibitor ML385. In conclusion, DP promotes DFU healing via activation of the Nrf2 pathway and inhibition of ferroptosis.
糖尿病足溃疡（DFU）伤口愈合延迟是截肢的主要原因，铁死亡会阻碍伤口恢复。血竭素（DP）是一种从血竭中提取的黄酮类化合物，已显示出抗炎和促进伤口愈合的特性，但其分子机制尚不清楚。本研究通过生物信息学和实验方法探讨DP在DFU治疗中的作用。通过高脂/高糖饮食和链脲佐菌素（STZ）诱导建立DFU大鼠模型，并在应用不同剂量的DP后监测伤口愈合情况。组织病理学分析和酶联免疫吸附测定（ELISA）评估组织变化、炎症标志物和生长因子。利用网络药理学和分子对接来确定核心靶点和信号通路，同时使用人脐静脉内皮细胞（HUVECs）进行体外试验。结果表明，DP通过增强胶原蛋白合成、血管生成和生长因子水平，同时降低炎症和活性氧（ROS）水平，以剂量依赖的方式加速DFU大鼠的伤口愈合。网络药理学和分子对接分析确定Nrf2介导的铁死亡信号通路是DP对DFU治疗作用的潜在关键机制。体外实验进一步表明，DP提高了细胞活力和迁移能力，同时降低了ROS和脂质过氧化水平，这些作用归因于Nrf2信号通路的激活。Nrf2抑制剂ML385显著减弱了这些结果。总之，DP通过激活Nrf2信号通路和抑制铁死亡促进DFU愈合。
