Dietary threonine prevented stress-related mucosal diseases in rats.

Stress-related mucosal disease (SRMD), or stress ulceration, is a group of conditions ranging from stress-related superficial gastric mucosal damage to deep gastric ulcers that are primarily correlated with mucosal ischemia, and pharmacologic interventions that optimize tissue perfusion or preserve defensive mucus aim to decrease the occurrence of conditions, such as gastric acidity, or enhance gastric defenses. However, the identification of multifactorial pathogenesis may be effective in preventing SMRD, and the use of stress prophylaxis is generally preferred. Since threonine is a component in the polymerization and synthesis of gastric mucin and possibly enhanced defense actions and lignin may provide structural support for defense and antioxidative function, we hypothesized that dietary intake of threonine and/or lignin can enhance defense against SRMD. The water immersion-restraint stress (WIRS) was used in rats and additional groups were pretreated with threonine alone or the combination of threonine and lignin. Based on gross and microscopic evaluations, threonine alone or the combination of threonine and lignin, a natural antioxidant, significantly reduced the development of SRMD (P < 0.05). According to molecular explorations, the levels of inflammatory mediators, such as interleukin (IL)-8, IL-6, IL-1ß, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ), all of which are mediators that play a significant role in controlling WIRS, significantly decreased in the groups pretreated with either threonine alone or the combination of threonine and lignin (P < 0.01). WIRS significantly increased apoptosis in the stomach. However, the apoptotic index significantly decreased with threonine pretreatment. According to periodic acid Schiff staining results, the expression of gastric mucin was significantly preserved in groups pretreated with threonine but remarkedly decreased in the WIRS group. The gastric heme oxygenase-1 levels significantly increased in the group treated with threonine. In conclusion, the dietary intake of threonine or the combination of threonine and lignin is effective in preventing SRMD.

Oligonol prevented the relapse of dextran sulfate sodium-ulcerative colitis through enhancing NRF2-mediated antioxidative defense mechanism.

Repeated bouts of ulcerative colitis featured troublesome course of inflammatory bowel disease leading to fatal colitis-associated cancer, which is strongly associated with oxidative stress and sustained inflammation. Since oligonol, low molecular weighted polyphenol extracted from fruit lychee, showed antioxidative and anti-inflammatory actions, we hypothesized that oligonolcan prevent relapse of colitis. We compared oligonol with current gold standard therapeutics, sulfasalazine in preventive efficacy of relapse. First, dextran sulfate sodium (DSS)-induced colitis were made following pretreatment with oligonol, 10, 50, and 100 mg/kg for 7 days to measure therapeutic effect of oligonol and relapse model via repeated DSS administration was made following with either 50 mg/kg oligonol or 30 mg/kg sulfasalazine to explore relapse preventing action of oligonol in C57BL/6 mice. Detailed changes in colon were measured to explain molecular mechanisms. Pretreatment of 10, 50, 100 mg/kg oligonol (p.o.), significantly reduced DSS-induced colitis; total pathologic scores, colon length, and clinical symptom scores (P < 0.05). Oligonol pretreatment significantly decreased the levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α) as well as nuclear factor-κB (NF-κB), c-Fos, and c-Jun in affected colon tissues, but the expression of heme oxygenase-1 (HO-1) and NADH: quinone oxidoreductase-1(NQO-1) as well as total antioxidant concentration (P < 0.005) was significantly increased with oligonol. A relapse model established with repeated DSS administration led to high mortality. However, oligonol significantly ameliorated exacerbations of colitis, while sulfasalazine did not (P < 0.01). Significantly decreased expressions of cyclooxygenase-2 (COX-2), TNF-α, and macrophages inhibition were relapse preventing actions of oligonal, but significant action of oligonol relevant to relapse prevention was either significantly increased expressions of NQO-1 or significantly preserved mucin (P < 0.05). Concerted anti-inflammatory, antioxidative, and host defense enhancing actions of oligonol can be applied during maintenance therapy of IBD to prevent relapse of IBD.

Host nuclear factor erythroid 2-related factor-2 defense system determines the outcome of dextran sulfate sodium-induced colitis in mice.

Administration of dextran sulfate sodium (DSS) in drinking water led to significant bout of colitis simulating ulcerative colitis of human. However, colitis usually developed 5 - 7 days after DSS administration. Therefore, we hypothesized host defense system might protect colitis up to 5 days of DSS administration. 2.5% DSS-induced colitis were administered to C57BL/6 mice and sequential measurements of pathology, cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κB), heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase-1 (NQO1), γ-glutamylcysteine synthetase (γ-GCS), nuclear factor erythroid 2-related factor-2 (Nrf2), and keap1 were done at 2, 6, 12, 24, 48, 96, 120, and 168 hour of DSS administration, respectively. DSS-induced colitis was repeated in either COX-2-/- or Nrf2-/- mice. On serial pathological analysis, significant colitis was noted after 120 h of DSS administration, during which both activations of COX-2/NF-κB and HO-1/Nrf2 were noted. Nrf2 activations after keap1 inactivation led to significant increases in HO-1 after 168 hours of DSS administration, when NF-κB nuclear translocation was noted. Significantly attenuated colitis was noted in DSS-challenged COX-2-/- mice, in which the levels of HO-1 were significantly decreased compared to DSS-challenged WT littermates (p < 0.01), while the levels of NQO1 were significantly increased. On DSS administration to Nrf2-/- mice, colitis was significantly aggravated (p < 0.01), in which the expressions of COX-2 as well as expressions of HO-1 and γ-GCS were significantly increased (p < 0.01). Reciprocal activations of inflammatory and antioxidative defense signaling after DSS administration might be prerequisite to make intestinal homeostasis and host defense Nrf2 system can determine colitis.