OBJECTIVES: To investigate the mechanism by which freeze-dried water extract of Lonicera japonica alleviates oxidative stress and improves post-ischemic heart failure in mice. METHODS: Bioinformatics analyses were carried out to identify the active constituents in Lonicera japonica, their target genes, and their enrichment pathways. Mouse models of ischemic heart failure established by left anterior descending (LAD) artery ligation were treated with different doses of freeze-dried water extract of Lonicera japonica, and the changes in cardiac function, myocardial pathology and expressions of the STAT3/PGC-1α axis were examined. In cultured H9C2 cells with oxygen-glucose deprivation (OGD), the effects of Lonicera japonica extract on cell viability, reactive oxygen species (ROS) production and apoptosis were evaluated, and its regulatory effects on STAT3 and PGC-1α expression were assessed using Western blotting and immunofluorescence staining; mass spectrometry was employed to analyze the tissue-penetrating components of Lonicera japonica extract, and the binding capacities of its major constituents to STAT3 and PGC-1α were simulated with molecular docking studies. RESULTS: In mice with ischemic heart failure, treatment with Lonicera japonica extract significantly improved the cardiac function and alleviated myocardial hypertrophy, inflammatory responses and collagen deposition. The treatment also restored cell viability of H9C2 cells with OGD and reduced cellular ROS production and cell apoptosis. Lonicera japonica extract significantly inhibited STAT3 activation and upregulated PGC-1α expression in H9C2 cells with OGD, and this effect was effectively attenuated by application of the STAT3 agonist Colivelin. Molecular docking results suggested that among the components of Lonicera japonica extract capable of entering the myocardial tissues, lonicerin, chlorogenic acid and 1,5-dicaffeoylquinic acid had strong binding affinity with STAT3 and PGC-1α. CONCLUSIONS: Lonicera japonica extract alleviates myocardial oxidative stress and improves heart failure in mice via the STAT3/PGC-1α axis, suggesting the value of Lonicera japonica in the treatment of heart failure. 目的: 探究金银花水提冻干粉通过STAT3/PGC-1α轴减轻氧化应激改善缺血后心衰的作用及其机制，评估其在心力衰竭治疗中的潜力。方法: 通过TCMSP网站筛选有效成分（OB≥30%且DL≥0.18），利用Swiss Target Prediction、GeneCards、DisGeNET、OMIM数据库获取作用靶点，借助STRING数据库（可信度0.4）、Cytoscape 3.10.0软件对靶点进行GO、KEGG分析;左前降支（LAD）结扎法建立缺血性心衰模型，随后给予不同剂量金银花干预，并进行心脏功能、病理学、分子生物学检测;H9C2细胞通过糖氧剥夺（OGD）建立细胞模型，观察金银花对细胞活力、ROS生成及凋亡的影响;Western blotting和免疫荧光检测金银花对STAT3、PGC-1α的调控作用;质谱分析金银花的入组织成分，分子对接研究其主要成分与STAT3和PGC-1α的结合能力。结果: 金银花水提冻干粉显著改善LAD小鼠心功能，减轻心肌肥大、炎症反应和胶原沉积（P<0.05），同时还能恢复OGD处理后H9C2细胞活力，减少ROS生成和细胞凋亡（P<0.001）;进一步实验显示金银花抑制STAT3激活，上调PGC-1α表达（P<0.001）;STAT3激动剂Colivelin可逆转金银花水提冻干粉的抗氧化应激效果;分子对接结果显示，金银花水提冻干粉入心肌组织成分中獐牙菜苷、绿原酸和1，5-二咖啡酰奎宁酸与STAT3和PGC-1α具有良好的结合能力（P<0.001）。结论: 本研究揭示金银花水提冻干粉通过STAT3/PGC-1α轴减轻氧化应激、改善心衰的机制，为金银花在心衰治疗中的应用提供了新的依据。.