Hydroxyproline Attenuates Dextran Sulfate Sodium‐Induced Colitis in Mice: Involvment of the NF‐κB Signaling and Oxidative Stress. Issue 21 (24th September 2018)

• Record Type: Journal Article
• Authors: Ji, Yun; Dai, Zhaolai; Sun, Shiqiang; Ma, Xiaoshi; Yang, Ying; Tso, Patrick; Wu, Guoyao; Wu, Zhenlong
• Is Part Of: Molecular nutrition & food research. Volume 62:Issue 21(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-09-24
• Subjects: colitis -- DSS -- hydroxyproline -- IBD -- inflammation -- lipopolysaccharide -- ROS; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201800494
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : Scope: Inflammatory bowel disease (IBD) is a chronic disease of gastrointestinal tract in which oxidative stress and overactivation of inflammatory response are implicated. The aim of the present study is to test the hypothesis that hydroxyproline (Hyp), an amino acid with an antioxidative property, attenuates dextran sulfate sodium (DSS)‐induced colitis in mice. Methods and results: Male C57BL/6 mice supplemented with or without 1% Hyp are subjected to 2.5% DSS in drinking water to induce colitis. Hyp attenuates the severity of colitis as evidenced by reduced disease activity index scores, decreased myeloperoxidase activity, histological damage, and apoptosis. Furthermore, DSS‐induced increases in reactive oxygen species accumulation, TNF‐α and IL−6 secretion, and malonyldialdehyde activity and a decrease in reduced glutathione in the colon are ameliorated by Hyp. The enhanced phosphorylation of STAT3 and NF−κB following DSS administration is mitigated by Hyp, which is also observed in LPS−treated RAW264.7 macrophages. Moreover, the inhibitory effect of Hyp on IL−6 expression is mainly mediated by the NF−κB signaling, because the induction of STAT3 and IL−6 by LPS is markedly reversed by Bay11‐7085, a specific inhibitor NF−κB. Conclusion: In summary, Hyp is a critical nutrient with an ability to attenuate DSS‐induced colonic damage in mice. This beneficial effect of Hyp is partially mediated by inhibiting the NF−κB/IL−6 signaling and the restoration of redox homeostasis. Abstract : Supplementation of hydroxyproline ameliorates colitis via inactivation of nuclear factor κB (NF−κB), and subsequent reduction in the expression of IL‐6 and phosphorylation of STAT3. The excessive reactive oxygen species (ROS) generated from macrophages and neutrophils induced by inflammatory responses can be neutralized by hydroxyproline, which contributes to reduce the activity of NF−κB and the restoration of redox homeostasis in the colon.