Protective effect of 7-hydroxyl-1-methylindole-3-acetonitrile on the intestinal mucosal damage response to inflammation in mice with DSS-induced colitis

• Published in: Chemico-biological interactions 2023-01, Vol.370, p.110316-110316, Article 110316
• Main Authors: Chung, Kyung-Sook, Park, Sang-Eun, Lee, Jung-Hun, Kim, Su-Yeon, Han, Hee-Soo, Lee, Yong Sup, Jung, Seang-Hwan, Jang, Eungyeong, Lee, Sangmin, Lee, Kyung-Tae
• Format: Article
• Language: English
• Subjects: 7-Hydroxyl-1-methylindole-3-acetonitrile; Animals; Colitis - chemically induced; Colitis - drug therapy; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - metabolism; Colon - pathology; Dextran Sulfate - toxicity; Disease Models, Animal; Drinking Water; DSS-Induced colitis; Inflammation - metabolism; Inflammatory cytokine; Membrane permeability; Mesalamine - pharmacology; Mesalamine - therapeutic use; Mice; Mice, Inbred C57BL; NF-kappa B - metabolism; Tight junction
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2022.110316

Ulcerative colitis (UC), a pathological condition of inflammatory bowel disease, is a chronic inflammatory disorder that involves an abnormal immune response and epithelial barrier dysfunction. Although we have previously reported the anti-inflammatory effects of 7-hydroxyl-1-methylindole-3-acetonitrile (7-HMIA), a synthesized analog of arvelexin on macrophages and paw edema, its anti-colitis effect and its mechanism are not known. In this study, colitis was induced in mice model by 4% (w/v) dextran sodium sulfate (DSS) solution in drinking water for 9 days. At the same time, from the first day of administering drinking water containing DSS, the animals were treated with 5-aminosalicylic acid (5-ASA), 75 mg/kg/day, orally) or 7-HMIA (10 or 20 mg/kg/day, intraperitoneally), depending on the experimental group, respectively. The studies were terminated on the tenth day of the experiment. Our data showed that 7-HMIA reduced the disease activity index and spleen/body weight (S/B) ratio, and improved the shortened colon length comparable to the effects of 5-ASA observed in the DSS-exposed mice. 7-HMIA, like 5-ASA, inhibited the histological damage, such as a thickened colonic muscle layer and shortened crypt length in the colon of the mice with DSS-induced colitis. 7-HMIA restored the tight junction-related proteins (occludin, claudin-1, and claudin-2) and epithelial-mesenchymal transition-mediated proteins (E-cadherin, N-cadherin, and vimentin) in the colon tissue of mice with DSS-induced colitis. Additionally, 7-HMIA (20 mg/kg/day) showed the inhibitory effects similar to that of 5-ASA on the myeloperoxidase activity, interleukin (IL)-6 production, and expression levels of inducible nitric oxide synthase (iNOS), and even showed greater inhibition of IL-1β production in the DSS-induced mice. Furthermore, the DSS-induced activation of nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) were effectively suppressed by 7-HMIA treatment like the effects of 5-ASA. Overall, our findings revealed that 7-HMIA decreased the severity of colitis by protecting the inflamed mucosal barrier by interfering with NF-κB and STAT3 activation. •7-HMIA is a synthesized analog of arvelexin.•7-HMIA relieves the clinical symptoms of DSS-induced colitis in mice.•7-HMIA protects epithelial barrier in the colon of DSS-induced colitis mice.•7-HMIA attenuates DSS-induced inflammatory response in the mice colon.