Lobenzarit Attenuates DSS-Induced Colitis by Reprogramming Immune Microenvironment and Mitochondrial Homeostasis

Background: The incidence of inflammatory bowel disease (IBD) is growing in the population. At present, the etiology of inflammatory bowel disease remains unclear, and there is no effective and low-toxic therapeutic drug. This study aimed to investigate the role of Lobenzarit (Lbz) in the treatment of colitis in mice as well as the underlying mechanism. Methods: In this experiment, colitis was induced in mice with dextran sulphate sodium (Dss). Subsequently, the role of Lbz in colitis and its underlying mechanisms were examined using H&E staining, TEM, ELISA, PCR, and other assays. Results: Lbz significantly attenuated the related symptoms of Dss-induced colitis in mice. In addition, Lbz suppressed neutrophil infiltration and restored macrophage polarization towards an anti-inflammatory state. Lbz also inhibited (p < 0.05) the activation of signaling pathways TLR4 and MAPK (51.61% decrease for TLR4 and 56.94% decrease for MAPK), reduced the release of inflammatory factors as it significantly decreased (p < 0.05) colonic IL-1β, TNF-α, IFN-γ, COX2, and VEGF (47.63, 42.49, 53.42, 58.74, and 61.28% decreases respectively) thereby attenuating the inflammatory response in mice. Lbz administration also restored the permeability of the intestinal barrier by increasing (p < 0.05) tight junction-associated proteins (claudin-1, occludin, and ZO-1 with a 5.36- and 2.26-fold increase for claudin-1 and ZO-1, respectively) and decreasing (p < 0.05) MALK levels by 53.51%. In addition, Lbz upregulated colonic Cytochrome C oxidase II, PDH, and ATP synthase levels and upregulated CD163, CD206, c-Maf, and PPAR-γ levels as compared to the DSS-treated group. Conclusions: Lbz has a repairing effect on Dss-induced colitis and may alleviate Dss-induced colitis by targeting the TLR4 pathway and promoting intestinal stem cell proliferation.