Zhang Liang, Ali Md Hasan, Jiang Chao, Fan Furong, Zhu Furong, Lu Yating, Jia Mengwei, Yin Haipeng, Wei Jianwang, Wu Dongsen, Chu Shenghui, Liu Min
Key Laboratory of Xinjiang Phytomedicine Resource and Utilisation, Ministry of Education, Institute for Safflower Industry Research, Pharmacy College, Collaborative Innovation Center for Efficient Safflower Production and Resource Utilization, Shihezi University, North 4th Road 221, Shihezi 832002, China.
Molecules. 2025 Jul 7;30(13):2886. doi: 10.3390/molecules30132886.
This study evaluated the in vitro anti-inflammatory activity of serotonin derivatives from safflower seed powder and elucidated their mechanism against ulcerative colitis using network pharmacology. Compounds were extracted and purified via silica gel column chromatography, Sephadex LH-20 and semi-preparative HPLC. Structural characterization employed NMR and UPLC-Q-TOF-MS/MS with literature comparisons. Anti-inflammatory efficacy was assessed in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Network pharmacology predicted targets, molecular docking analyzed binding interactions and molecular dynamics simulations assessed complex stability. Eleven serotonin derivatives were isolated; N-trans-Feruloyl-3,5-dihydroxyindolin-2-one () and Bufoserotonin A () were identified in safflower seed meal for the first time. Compounds , - and significantly reduced inflammatory factors, with N-feruloyl serotonin (, FS) showing the strongest activity. Mechanistic studies revealed FS targets key molecules (STAT3, EGFR, ESR1, PTGS2, NF-κB1, and JUN), modulating PI3K-Akt, MAPK and cancer-related pathways. Molecular dynamics simulations confirmed FS-EGFR complex stability. Thus, two novel derivatives were isolated and FS demonstrated significant anti-inflammatory and potential anti-ulcerative colitis effects through multi-target, multi-pathway synergy, providing a foundation for developing safflower seed meal therapeutics.
本研究评估了红花籽粉中5-羟色胺衍生物的体外抗炎活性，并利用网络药理学阐明了它们对抗溃疡性结肠炎的机制。通过硅胶柱色谱、葡聚糖凝胶LH-20和半制备型高效液相色谱对化合物进行提取和纯化。采用核磁共振和超高效液相色谱-四极杆-飞行时间串联质谱并与文献比较进行结构表征。在脂多糖（LPS）诱导的RAW 264.7巨噬细胞中评估抗炎效果。网络药理学预测靶点，分子对接分析结合相互作用，分子动力学模拟评估复合物稳定性。分离出11种5-羟色胺衍生物；首次在红花籽粕中鉴定出N-反式阿魏酰基-3,5-二羟基吲哚-2-酮（）和蟾蜍色胺A（）。化合物、和显著降低炎症因子，其中N-阿魏酰基5-羟色胺（，FS）活性最强。机制研究表明，FS靶向关键分子（STAT3、EGFR、ESR1、PTGS2、NF-κB1和JUN），调节PI3K-Akt、MAPK和癌症相关通路。分子动力学模拟证实了FS-EGFR复合物的稳定性。因此，分离出两种新型衍生物，FS通过多靶点、多途径协同作用表现出显著的抗炎和潜在的抗溃疡性结肠炎作用，为开发红花籽粕治疗药物奠定了基础。
