Maresin 1 alleviates dextran sulfate sodium-induced ulcerative colitis by regulating NRF2 and TLR4/NF-kB signaling pathway |
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| Affiliation: | 1. Department of Spleen and Stomach, Shannxi Traditional Chinese Medicine Hospital, Xi’an 710018, China;2. Department of Emergency, The Second Affiliated Hospital of Xi''an Jiaotong University, Xi’an 710004, China;3. Department of Gastroenterology, The Affiliated Hospital of Northwest University, Xi’an No. 3 Hospital, Xi’an 710018, China;4. International Medicine Services, The Affiliated Hospital of Northwest University, Xi’an No. 3 Hospital, No. 10 Fengcheng Third Road, Weiyang District, Xi’an 710018, China;1. Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;2. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;3. Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;4. Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;5. Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;1. Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, 71666, Saudi Arabia;2. Department of Anatomy, Mansoura Faculty of Medicine, Mansoura University, Egypt;3. Department of Biochemistry, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt;4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia;5. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt;6. Department of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt |
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| Abstract: | ObjectiveUlcerative colitis (UC) is one of the most common gastrointestinal diseases, characterized as a chronic, relapsing inflammation that causes damage to the colonic mucosa. Maresin 1 (MaR1), a specialized proresolving mediator, has powerful anti-inflammatory activity that prevents the occurrence of various inflammatory diseases. The aim of this study was to explore the role and potential mechanism of MaR1 in DSS-induced ulcerative colitis.MethodsIn the present study, we established dextran sulfate sodium (DSS)-induced ulcerative colitis rat model in vivo. Rats with colitis received tail vein injection of MaR1, with or without intraperitoneal injection of ML385. The changes of body weight, colon length, disease activity index (DAI), colonic histopathology, inflammatory cytokines, the activity of myeloperoxidase (MPO) and reactive oxygen species (ROS), and infiltration of macrophages expressing F4/80 were analyzed for the evaluation of colitis severity. In addition, protein expressions were detected using western blot.ResultsMaR1 significantly reduced inflammatory cytokines production, and restored body weight, DAI and colonic histopathology. Besides, MaR1 improved the expression of tight junction (TJ) proteins and reduced the infiltration of neutrophil and macrophages, as well as a decreased activity of MPO and ROS. Meanwhile, MaR1 activated Nrf2 signaling and decreased toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) activation. Furthermore, ML385, an inhibitor of Nrf2, significantly reversed the protective effect of MaR1.ConclusionMaR1 play a protective role in DSS-induced colitis by activating Nrf2 signaling and inactivating Nrf2-mediated TLR4/NF-κB signaling pathway, which mediate proinflammatory mediators and intestinal TJ proteins in rats, providing novel insights into the therapeutic strategy of colitis. |
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| Keywords: | Maresin 1 Ulcerative colitis Nuclear factor erythroid 2-related factor 2 Tight junction Toll-like receptor 4 Nuclear factor-κB |
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