Higenamine improves DSS-induced ulcerative colitis in mice through the Galectin-3/TLR4/NF-κB pathway

Ulcerative colitis (UC) is an inflammatory disease of the colon and tends to relapse. Higenamine (HG) has anti-inflammatory, antioxidant and anti-apoptotic activities. This study aimed to investigate the role of HG in the treatment of UC as well as the underlying mechanism. In vivo and in vitro models of UC were respectively established in dextran sodium sulfate (DSS)-induced mice and DSS-induced NCM460 cells. The weight and disease performance and disease activity index (DAI) of mice were recorded every day. The colon length was measured and pathological changes of colon tissues were observed by HE staining. The apoptosis of colon cells in mice was detected by Tunel assay and FITC-dextran was used to detect intestinal permeability in mice. The MPO activity and expression of tight junction proteins and Galectin-3/TLR4/NF-κB pathway related proteins in colon tissues and cells were detected by MPO assay kit and western blot. The levels of TNF-α, IL-1β, IL-6 and IL-10 in serum and cells, and levels of DAO and D-LA in serum were all detected by assay kits. The viability and apoptosis of NCM460 cells were analyzed by CCK-8 assay and flow cytometry analysis, and permeability of NCM460 monolayers was detected by TEER measurement. As a result, HG improved the weight, DAI, colon length and pathological changes of DSS-induced UC mice. HG alleviated DSS-induced colon inflammation, inhibited DSS-induced apoptosis of mouse colonic epithelial cells and restored the integrity of the mucosa barrier in mice. In addition, HG suppressed the Galectin-3/TLR4/NF-κB signaling pathway in DSS-induced UC mice. Similarly, HG improved viability and epithelial barrier function, and suppressed the apoptosis and inflammation of DSS-induced NCM460 cells by inhibiting the Galectin-3/TLR4/NF-κB signaling pathway. Galectin-3 overexpression could reverse the effect of HG on DSS-induced NCM460 cells. In conclusion, HG improved DSS-induced UC through the inactivation of Galectin-3/TLR4/NF-κB pathway in vivo and in vitro. The data are available from the corresponding author on reasonable request.