The Effect of 7-Hydroxycoumarin on Dextran Sulfate Sodium-induced Ulcerative Colitis.
الكلمات الدالة
نبذة مختصرة
7-Hydroxycoumarin (HC) or Umbelliferone exerts many beneficial effects, ie. antioxidant, anti-tumour, anti-inflammatory and immunomodulatory activities. We hypothesized that HC had mitigating properties on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice, via suppression of inflammation. The induction of UC in mice was achieved by the administration of 3.5% DSS in drinking water for 7 consecutive days. Administration of HC to DSS-induced mice ameliorated the loss of body weight, reduced diarrhoea and gross bleeding and showed a significant reduction in the disease activity index (DAI). Further, it alleviated the DSS-induced shortening of colon length. Also, HC ameliorated mucosal damage, colonic oedema and infiltration of neutrophil into colonic intestinal tissue in response to damage caused by DSS. The increased expressions of inflammatory factors such as tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-17, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), and decreased expression of anti-inflammatory marker IL-10. Administration of HC reduced the above said inflammatory factors significantly. In addition, HC reduced the level ofTBARS, increased the activities of antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD). We also analysed the nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) expression in the experimental mice. It was found that HC could activate the Nrf2 and its downstream targets. In conclusion, HC treatment protects the colon from DSS-induced pathology, which is associated with enhanced enzymatic antioxidants and the activation of Nrf2 signalling. Thus, dietary HC can be beneficial to UC patients as a complementary therapeutic agent. This article is protected by copyright. All rights reserved.