Published online Apr 21, 2019. doi: 10.3748/wjg.v25.i15.1865
Peer-review started: January 4, 2019
First decision: January 30, 2019
Revised: March 5, 2019
Accepted: March 15, 2019
Article in press: March 16, 2019
Published online: April 21, 2019
Clinical treatment of ulcerative colitis consists of drugs that are both expensive and have side effects. Unconjugated bilirubin (UCB) has gained recent prominence for its anti-inflammatory and antioxidant properties. How UCB influences UC remains unresolved.
Patients with UC require lifelong treatment, and drugs for UC are linked to many adverse effects. Therefore, there is an urgent need to develop effective and safe drugs for UC.
To investigate the significance of UCB in intestinal barrier function and immune inflammation of mice with dextran sodium sulfate (DSS)-induced colitis.
UC was induced by 3% (w/v) DSS in drinking water for 6 d followed by untreated water for 2 d. Concurrently, colitis mice were administered 0.2 mL UCB (400 μM) by intra-gastric gavage for 7 d. Disease activity index (DAI) was monitored daily. The length of the colon and weight of the spleen were recorded. Serum level of D-lactic acid, intestinal digestive proteases activity, and changes in gut flora were analyzed. In addition, colonic specimens were analyzed by histology and for expression of inflammatory markers and proteins.
UCB significantly relieved the severity of colitis, including lower DAI, longer colon length, and smaller spleen weight (P < 0.001). UCB inactivated digestive proteases (P < 0.01), increased expression of tight junction protein occludin (P < 0.001), decreased serum level of D-lactate (P < 0.001), and lowered histopathological score and activity of myeloperoxidase compared with those in colitis mice (P < 0.001). UCB also regulated the intestinal microbiota, inhibited expression of tumor necrosis factor (TNF)-α and interleukin-1β (P < 0.001), decreased expression of Toll-like receptor (TLR) 4 (P < 0.001) and myeloid differentiation primary response gene 88 (P < 0.05), and increased expression of TNF-receptor-associated factor 6 (P < 0.05) and IκBα (P < 0.05) in the colon.
UCB has a beneficial regulatory effect on intestinal barrier function and regulates normal intestinal homeostasis, and can suppress inflammation via the TLR4/NF-κB signaling pathway. This provides a theoretical basis for use of UCB as a clinical drug.
UCB plays a pivotal role in intestinal innate immunity and inflammation. Thus, the findings of this study indicate a novel potential mechanism by which UCB can treat UC. More studies are needed to investigate the effect of UCB on chronic UC or colon cancer.