Table 2_Nymphaea “Eldorado” flower extract targets serpine 1 to attenuate inflammatory and antioxidant crosstalk in zebrafish.xlsx

Chronic inflammation and oxidative stress are pivotal drivers of pathological conditions, necessitating safer plant-derived therapeutic alternatives. This study elucidates the anti-inflammatory and antioxidant mechanisms of Nymphaea “Eldorado” flower water extract (NEWE) in a zebrafish (Danio rerio) model of copper sulfate (CuSO4)-induced inflammation. NEWE (25–100 μg/mL) attenuates CuSO4-triggered neutrophil migration and oxidative stress by downregulating proinflammatory genes (il1b, ptgs2a/b) and reducing reactive oxygen species (ROS) production. Transcriptomic profiling identified 339 differentially expressed genes (DEGs), enriched in cytokine signaling and redox regulation, with serpine1, stat3, and mmp9 emerging as key regulatory hubs. Widely targeted metabolomics revealed 891 bioactive compounds, including flavonoids and phenylpropanoids, with network pharmacology predicting multi-target interactions involving inflammatory and oxidative stress pathways. Molecular docking confirmed binding affinities between protocatechuic acid, L-pyroglutamic acid, and Serpine1’s active site, indicating direct interference with inflammation modulation. Collectively, these results establish NEWE as a polypharmacological agent that disrupts inflammation-oxidative stress crosstalk primarily through Serpine1-mediated pathways, offering a molecular foundation for plant-derived interventions against chronic inflammatory diseases.

慢性炎症与氧化应激是多种病理状态的关键驱动因素，因此亟需安全性更高的植物源治疗替代方案。本研究以硫酸铜（CuSO4）诱导炎症的斑马鱼（Danio rerio）模型为载体，阐明了"埃尔多拉多"睡莲花水提取物（NEWE）的抗炎与抗氧化机制。在25~100 μg/mL的剂量范围内，NEWE可通过下调促炎基因（il1b、ptgs2a/b）的表达、减少活性氧（ROS）生成，缓解硫酸铜诱导的中性粒细胞迁移与氧化应激。转录组分析鉴定出339个差异表达基因（DEGs），这些基因显著富集于细胞因子信号通路与氧化还原调控过程，其中serpine1、stat3及mmp9为核心调控枢纽。广泛靶向代谢组学检测到891种生物活性成分，涵盖黄酮类与苯丙素类化合物；网络药理学分析预测其可通过多靶点作用于炎症与氧化应激相关通路。分子对接实验证实，原儿茶酸、L-焦谷氨酸可与Serpine1的活性位点结合，提示其可直接干预炎症调控过程。综上，本研究结果表明NEWE是一种多靶点药理活性物质，主要通过Serpine1介导的通路干扰炎症-氧化应激串扰，为植物源慢性炎症疾病干预手段提供了分子层面的理论基础。