Ophiopogonin D Inhibiting Epithelial NF-κB Signaling Pathway Protects Against Experimental Colitis in Mice.

Abstract

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.