Wei Wu-Han, Bai Yuan-Ling, Zhu Dong, Zhang Jing-Yu, Yin Qi-Chuan, Li Qiang, Shen Cai-Qi, Jin Pei-Sheng
The First Clinical Medical College, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China.
Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100144, China.
World J Diabetes. 2025 Apr 15;16(4):101916. doi: 10.4239/wjd.v16.i4.101916.
Diabetic foot ulcers (DFU) are estimated to affect about 18.6 million people worldwide annually. The pathogenesis of DFU is complex, and the available drugs are not effective. Dl-3-n-butylphthalide (NBP) is a synthetic mixture of racemates used in China for the treatment of ischemic stroke. It was initially isolated from the seeds of Linn, with studies showing its potential role in treating diabetes and its complications.
To predict and validate the mechanism by which NBP treats DFU.
Network pharmacological analysis was performed to identify pharmacological targets and signaling pathways mediating the treatment effect of NBP on DFU. and experiments were conducted to validate the therapeutic effects and mechanisms of NBP on DFU.
Network pharmacology analysis identified 26 pharmacological targets of NBP and predicted that NBP could treat DFU partially by modulating apoptosis and vascular signaling pathways. Results from animal experiments showed that NBP significantly improved DFU by increasing neovascularization and fibroblast proliferation. tests demonstrated that NBP treatment promoted the migration and proliferation of human umbilical vein endothelial cells and human dermal fibroblasts, while inhibiting the apoptosis of human umbilical vein endothelial cells, human dermal fibroblasts, and human keratinocytes cells.
This study found that NBP could treat DFU by decreasing the rate of apoptosis and increasing angiogenesis the advanced glycation end products-receptor of advanced glycation end products signaling pathway and binding to the heme oxygenase 1, caspase 3, B cell leukemia/lymphoma 2, brain derived neurotrophic factor, and nuclear factor erythroid 2 L2 genes.
据估计，全球每年约有1860万人受糖尿病足溃疡（DFU）影响。DFU的发病机制复杂，现有药物效果不佳。丁苯酞（NBP）是一种在中国用于治疗缺血性中风的消旋体合成混合物。它最初从芹菜籽中分离出来，研究表明其在治疗糖尿病及其并发症方面具有潜在作用。
预测并验证NBP治疗DFU的机制。
进行网络药理学分析，以确定介导NBP对DFU治疗作用的药理靶点和信号通路。并开展实验验证NBP对DFU的治疗效果及机制。
网络药理学分析确定了NBP的26个药理靶点，并预测NBP可通过调节细胞凋亡和血管信号通路部分治疗DFU。动物实验结果表明，NBP通过增加新血管形成和成纤维细胞增殖显著改善DFU。体外实验表明，NBP治疗可促进人脐静脉内皮细胞和人皮肤成纤维细胞的迁移和增殖，同时抑制人脐静脉内皮细胞、人皮肤成纤维细胞和人角质形成细胞的凋亡。
本研究发现，NBP可通过降低凋亡率和增加血管生成，作用于晚期糖基化终产物-晚期糖基化终产物受体信号通路，并与血红素加氧酶1、半胱天冬酶3、B细胞淋巴瘤/白血病-2、脑源性神经营养因子和核因子红细胞2相关因子2基因结合来治疗DFU。
