Xu Penghong, Qian Yuping, Xu Guo, Chu Jianlin, He Bingfang
School of Pharmaceutical Sciences, Nanjing Tech University, 30 Puzhunan Road, Jiangbei New Area, Nanjing 211800, China.
College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 Puzhunan Road, Jiangbei New Area, Nanjing 211800, China.
Phytomedicine. 2025 Apr;139:156475. doi: 10.1016/j.phymed.2025.156475. Epub 2025 Feb 5.
Inflammatory bowel disease (IBD), a chronic inflammatory condition categorized into ulcerative colitis (UC) and Crohn's disease (CD), affects a growing global patient population. Despite the prevalence, clinically there is a scarcity of effective therapeutic agents.
This study investigated the therapeutic effects of fructosyl mangiferin (FM) on UC and elucidated its underlying mechanisms through in vivo and in vitro experiments.
In vivo, a UC model of C57BL/6J mice was established via dextran sulfate sodium (DSS) induction, and the therapeutic effects were assessed through intragastric administration. In vitro, the murine macrophage cell line RAW264.7 was stimulated with lipopolysaccharide (LPS) to establish an M1 polarization model and introduced to explore the role of FM in immune cells. Molecular docking was further employed to investigate the specific molecular mechanisms of FM.
In vivo experimental findings indicate that FM, like mangiferin (M), preserves mucin secretion and the expression of occludin protein, and both significantly impede the progression of fibrosis associated with colitis. Additionally, FM effectively suppresses M1 macrophage polarization and exerts a pronounced inhibitory effect on the adaptive immune response, outperforming M in mitigating UC. In vitro results corroborate FM's inhibitory action on M1 polarization. Molecular docking studies identified FM as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor, aligning with western blot analyses from both in vivo and in vitro experiments.
In conclusion, following fructosylation, FM exhibits remarkable anti-inflammatory and colonic protective effects. FM's ability to control the progression of UC offers a novel strategy for its potential treatment, warranting further investigation into its clinical application.
炎症性肠病（IBD）是一种慢性炎症性疾病，分为溃疡性结肠炎（UC）和克罗恩病（CD），全球患病人数不断增加。尽管患病率较高，但临床上有效的治疗药物却很匮乏。
本研究通过体内和体外实验，研究了果糖基芒果苷（FM）对UC的治疗作用，并阐明其潜在机制。
在体内，通过葡聚糖硫酸钠（DSS）诱导建立C57BL/6J小鼠UC模型，并通过灌胃给药评估治疗效果。在体外，用脂多糖（LPS）刺激小鼠巨噬细胞系RAW264.7建立M1极化模型，以探讨FM在免疫细胞中的作用。进一步采用分子对接研究FM的具体分子机制。
体内实验结果表明，FM与芒果苷（M）一样，能保留粘蛋白分泌和闭合蛋白的表达，两者均能显著阻碍结肠炎相关纤维化的进展。此外，FM能有效抑制M1巨噬细胞极化，对适应性免疫反应有明显的抑制作用，在减轻UC方面优于M。体外实验结果证实了FM对M1极化的抑制作用。分子对接研究确定FM为潜在的信号转导和转录激活因子3（STAT3）抑制剂，这与体内和体外实验的蛋白质印迹分析结果一致。
总之，果糖基化后，FM具有显著的抗炎和结肠保护作用。FM控制UC进展的能力为其潜在治疗提供了一种新策略，值得进一步研究其临床应用。
