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P028 Oligonol attenuates dextran sulfate sodium-induced colitis and reduces flare-UP in mice by enhancing host defense mechanism

Kim K.-J.*1, Park J.-M.2, Han Y.-M.2, Lee S.G.2, Shin S.A.2, Hahm K.-B.2

1Asan Medical Center, Gastroenterology, Seoul, South Korea 2Cha Bundang Medical Center, Cha University, Department of Gastroenterology, Seongnam-Si, South Korea

Background

Oxidative injury plays a role in the pathogenesis of inflammatory bowel disease (IBD). Oligonol, oligomerized low molecular weighted-polyphenols, have been demonstrated anti-oxidative and anti-inflammatory properties. We investigated anti-inflammatory effects of oligonol in 2 protocols of a dextran sulfate sodium (DSS)-induced colitis mouse model independently: acute colitis and repeated colitis.

Methods

DSS-induced colitis male C57BL/6 mice were made following pretreatment with different dosages of oligonol for 7 days (acute colitis model). In the second protocol, once the acute colitis had been induced with 3% DSS, sham water, oligonol (50mg/kg), and sulfasalazine (30mg/kg) were given during 2 weeks after the first DSS administration in each group. Then, 3% DSS was given again after the first DSS administration. Colitis was evaluated with macroscopic and microscopic findings.

Results

In the acute colitis model, pretreatment of 10, 50, 100mg/kg oligonol po reduced total pathologic scores significantly (p<0.05). Along with gross and pathological improvement, oligonol decreased the levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α as well as NF-κB, c-Fos, and c-Jun. Also, oligonol enhanced the expression of heme oxygenase (HO)-1 and NADH: quinone oxidoreductase-1 (NQO-1), and increased total antioxidant concentration significantly (p<0.005). In repeated colitis model, oligonol ameliorated exacerbations of colitis, whereas sulfasalazine did not (p<0.01). The level of COX-2, TNF-α were much lower, and induction of HO-1 and NQO1 were increased significantly in oligonol group, compared with in sulfasalazine group.

Conclusion

These results suggest that oligonol could be possibly protective against experimentally induced colitis through enhancing host defense mechanism. Thus, oligonol may be useful for the treatment of human IBD.