The sustained activation of the nuclear factor κB (NF-κB) signaling pathway has been observed in human inflammatory bowel disease (IBD). Ophiopogonin D (OP-D) is a small molecular compound isolated from Ophiopogon japonicus, a widely used herbal remedy. In this study, dextran sodium sulfate was used to make a mouse model of experimental colitis and verify the effect of OP-D on the mouse model of experimental colitis. Small molecule-protein molecular docking approaches were also used to discover the mechanisms underlying the OP-D-induced regulation of colitis. In colitis, the OP-D can inhibit the apoptosis of intestinal mucosa cells, restore the intestinal barrier, and alleviate inflammation. The molecular docking simulations showed that OP-D had a high affinity with the REL-homology domain of NF-κB-p65 that affected its translocation to the nucleus. In a cell study, the effects of OP-D on inflammation and barrier dysfunction were significantly decreased by a small interfering RNA targeting NF-κB-p65. Further, the LPS-induced increase in NF-κB-p65 in the nucleus was also significantly inhibited by OP-D. OP-D alleviated experimental colitis by inhibiting NF-κB. New insights into the pathogenesis and treatment options of colitis are provided through this study.

已在人类炎症性肠病 (IBD) 中观察到核因子 κB (NF-κB) 信号通路的持续激活。麦冬素 D (OP-D) 是一种从麦冬中分离得到的小分子化合物，一种广泛使用的草药。本研究采用葡聚糖硫酸钠制作实验性结肠炎小鼠模型，验证OP-D对实验性结肠炎小鼠模型的影响。小分子-蛋白质分子对接方法也用于发现 OP-D 诱导的结肠炎调节的机制。在结肠炎中，OP-D可以抑制肠黏膜细胞凋亡，恢复肠屏障，减轻炎症。分子对接模拟表明，OP-D 与影响其易位到细胞核的 NF-κB-p65 的 REL 同源域具有高亲和力。在一项细胞研究中，靶向 NF-κB-p65 的小干扰 RNA 显着降低了 OP-D 对炎症和屏障功能障碍的影响。更远，OP-D也显着抑制LPS诱导的细胞核中NF-κB-p65的增加。OP-D 通过抑制 NF-κB 减轻实验性结肠炎。本研究提供了对结肠炎发病机制和治疗方案的新见解。