Mu Xingrui, Chen Jitao, Zhu Huan, Deng Junyu, Wu Xingqian, He Wenjie, Ye Penghui, Gu Rifang, Wu Youzhi, Han Felicity, Nie Xuqiang
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, No. 6 West Xuefu Road, Xinpu New District, Zunyi 563006, China.
College of Pharmacy, Zunyi Medical University, No. 6 West Xuefu Road, Xinpu New District, Zunyi 563006, China.
Burns Trauma. 2025 Mar 10;13:tkaf009. doi: 10.1093/burnst/tkaf009. eCollection 2025.
Diabetic wounds pose significant clinical challenges due to impaired healing processes, often resulting in chronic, nonhealing ulcers. Asiaticoside (AC), a natural triterpene derivative from , has demonstrated notable anti-inflammatory and wound-healing properties. However, the synergistic effects of nitric oxide (NO)-a recognized promoter of wound healing-combined with AC in treating diabetic wounds remain inadequately explored.
Ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was utilized to identify differential metabolites and dysregulated metabolic pathways associated with diabetic wounds. Molecular docking analyses were conducted to confirm the binding affinity of AC to key therapeutic targets. The effects of asiaticoside-nitric oxide hydrogel (ACNO) on gene and protein expression were evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. experiments using sarcoma (SRC) agonists and inhibitors were performed to investigate the impact of ACNO therapy on the expression of SRC, STAT3, and other proteins in HaCaT cells.
Metabolomic profiling revealed that diabetic wounds in mice exhibited marked metabolic dysregulation, which was attenuated by ACNO treatment. Key metabolites modulated by ACNO included mandelic acid, lactic acid, and 3-hydroxyisovaleric acid. The primary metabolic pathways involved were methyl histidine metabolism and the malate-aspartate shuttle. Immunofluorescence staining confirmed that ACNO therapy enhanced angiogenesis, promoted cellular proliferation, and facilitated diabetic wound closure. RT-qPCR data demonstrated that ACNO regulated the transcription of critical genes (, , , and ). Notably, ACNO attenuated SRC/STAT3 pathway activation while concurrently upregulating EGFR and VEGFA expression.
These findings emphasize the therapeutic potential of ACNO hydrogel in diabetic wound healing through the modulation of metabolic pathways and the SRC/STAT3 signaling axis. By correlating altered metabolites with molecular targets, this study elucidates the pharmacodynamic foundation for ACNO's preclinical application and provides valuable insights into the development of targeted therapies for diabetic wound management.
糖尿病伤口由于愈合过程受损，常导致慢性、不愈合溃疡，给临床带来重大挑战。积雪草苷（AC）是一种从[来源未提及]提取的天然三萜衍生物，已显示出显著的抗炎和伤口愈合特性。然而，一氧化氮（NO）——一种公认的伤口愈合促进剂——与积雪草苷联合治疗糖尿病伤口的协同作用仍未得到充分探索。
采用超高效液相色谱-串联质谱（UPLC-MS/MS）鉴定与糖尿病伤口相关的差异代谢物和失调的代谢途径。进行分子对接分析以确认积雪草苷与关键治疗靶点的结合亲和力。使用逆转录-定量聚合酶链反应（RT-qPCR）和蛋白质印迹法评估积雪草苷-一氧化氮水凝胶（ACNO）对基因和蛋白质表达的影响。使用肉瘤（SRC）激动剂和抑制剂进行实验，以研究ACNO疗法对HaCaT细胞中SRC、STAT3和其他蛋白质表达的影响。
代谢组学分析表明，小鼠糖尿病伤口表现出明显的代谢失调，ACNO治疗可减轻这种失调。ACNO调节的关键代谢物包括扁桃酸、乳酸和3-羟基异戊酸。涉及的主要代谢途径是甲基组氨酸代谢和苹果酸-天冬氨酸穿梭。免疫荧光染色证实，ACNO疗法可增强血管生成、促进细胞增殖并促进糖尿病伤口愈合。RT-qPCR数据表明，ACNO调节关键基因（[基因名称未提及]、[基因名称未提及]、[基因名称未提及]和[基因名称未提及]）的转录。值得注意的是，ACNO减弱了SRC/STAT3途径的激活，同时上调了EGFR和VEGFA的表达。
这些发现强调了ACNO水凝胶通过调节代谢途径和SRC/STAT3信号轴在糖尿病伤口愈合中的治疗潜力。通过将改变的代谢物与分子靶点相关联，本研究阐明了ACNO临床前应用的药效学基础，并为糖尿病伤口管理的靶向治疗开发提供了有价值的见解。
