Sophocarpine Alleviates Inflammation-induced Colonic Epithelial Barrier Dysfunction in Ulcerative Colitis

Background Sophocarpine, a quinoline alkaloid derived from Sophora alopecuroides L., is known for its anti-inflammatory effects. These effects are achieved by modulating both nuclear factor-κB (NF-κB) pathway and node-like receptors pyrin domain containing 3 (NLRP3) inflammasome. However, whether sophocarpine could alleviate colonic inflammation requires further exploration. Objectives The present work focused on investigating the potential of sophocarpine for treating colonic epithelial barrier dysfunction in ulcerative colitis. Materials and Methods An inflammatory model was initially developed using human colorectal adenocarcinoma cells (Caco-2) induced by lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α), which was used for investigating how sophocarpine affected inflammation-mediated colonic epithelial barrier function and monitoring levels of inflammatory responses. Besides, the colonic epithelial barrier integrity was evaluated through measuring transepithelial/transendothelial electrical resistance (TEER). Lastly, we conducted Western blotting for assessing zonula occludens-1 (ZO-1), claudin-1, p65, p-p65, IκBα, p-IκBα, MLC, p-MLC, and myosin light chain kinase (MLCK) protein levels. Besides, the beneficial effect of sophocarpine was also evaluated in a mouse mode of ulcerative colitis. Results Upon LPS stimulation, Caco-2 cells exhibited enhanced TNF-α and interleukin (IL)-1β levels, along with reduced IL-4 and IL-10 levels, decreased TEER values, increased fluorescein isothiocyanate (FITC)-dextran concentrations, and suppressed ZO-1 and claudin-1 protein levels. In contrast, sophocarpine treatment at varying concentrations attenuated the detrimental effects of LPS induction. Notably, sophocarpine could reverse TNF-α-induced colonic epithelial barrier dysfunction through significantly decreasing p65, IκBα, and MLC protein phosphorylation levels within LPS-treated Caco-2 cells. Sophocarpine administration also mitigated inflammatory damages within the ulcerative colitis mouse model. Conclusion According to these findings, sophocarpine prevents inflammatory damage in the colonic epithelial barrier by targeting the NF-κB/MLCK/MLC signaling pathway, indicating a novel intervention strategy to ameliorate ulcerative colitis.