Autor: |
Wei J; Department of Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA.; Department of Pediatrics, Shanxi Medical University, Taiyuan 030001, China., Tao G; Department of Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA., Xu B; Department of Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA., Wang K; Department of Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA.; Department of Gastrointestinal Surgery, The First Hospital of China Medical University, Shenyang 110001, China., Liu J; Department of Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA.; Department of General Surgery, The People's Hospital of Liuyang City, Liuyang 410300, China., Chen CH; Department of Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA., Dunn JCY; Department of Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA., Currie C; R&D Department, Hofseth BioCare AS, 6003 Aalesund, Norway., Framroze B; Department of Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA.; R&D Department, Hofseth BioCare AS, 6003 Aalesund, Norway., Sylvester KG; Department of Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA. |
Abstrakt: |
Inflammatory bowel diseases (IBD) are chronic, recurring gastrointestinal diseases that severely impair health and quality of life. Although therapeutic options have significantly expanded in recent years, there is no effective therapy for a complete and permanent cure for IBD. Well tolerated dietary interventions to improve gastrointestinal health in IBD would be a welcome advance especially with anticipated favorable tolerability and affordability. Soluble protein hydrolysate (SPH) is produced by the enzymatic hydrolysis of commercial food industry salmon offcuts (consisting of the head, backbone and skin) and contains a multitude of bioactive peptides including those with anti-oxidant properties. This study aimed to investigate whether SPH ameliorates gastrointestinal injury in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Mice were randomly assigned to four groups: Control (no colitis), Colitis, Colitis/CP (with control peptide treatment), and Colitis/SPH (with SPH treatment). Colitis was induced by cutaneous sensitization with 1% TNBS on day -8 followed by 2.5% TNBS enema challenge on day 0. Control peptides and SPH were provided to the mice in the Colitis/CP or Colitis/SPH group respectively by drinking water at the final concentration of 2% w / v daily from day -10 to day 4. Then, the colon was harvested on day 4 and examined macro- and microscopically. Relevant measures included disease activity index (DAI), colon histology injury, immune cells infiltration, pro- and anti-inflammatory cytokines and anti-oxidative gene expression. It was found that SPH treatment decreased the DAI score and colon tissue injury when compared to the colitis-only and CP groups. The protective mechanisms of SPH were associated with reduced infiltration of CD4 + T, CD8 + T and B220 + B lymphocytes but not macrophages, downregulated pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-6), and upregulated anti-inflammatory cytokines (transforming growth factor-β1 and interleukin-10) in the colon tissue. Moreover, the upregulation of anti-oxidative genes, including ferritin heavy chain 1, heme oxygenase 1, NAD(P)H quinone oxidoreductase 1, and superoxide dismutase 1, in the colons of colitis/SPH group was observed compared with the control peptide treatment group. In conclusion, the protective mechanism of SPH is associated with anti-inflammatory and anti-oxidative effects as demonstrated herein in an established mice model of colitis. Clinical studies with SPH as a potential functional food for the prevention or as an adjuvant therapy in IBD may add an effective and targeted diet-based approach to IBD management in the future. |