P104 Icariin Attenuates Intestinal Inflammation through Inhibition of the Nuclear Factor-ĸB signaling

Soh, H.(1);Park, S.(2);Lee, H.J.(1);Koh, S.J.(1);Im, J.P.(1);Kim, J.S.(1);

(1)Seoul National University College of Medicine, Department of Internal Medicine and Liver Research Institute, Seoul, Korea- Republic Of;(2)Incheon Sejong Hospital, Department of Internal Medicine, Incheon, Korea- Republic Of;

Background

Icariin is a natural flavonoid glucoside from plants in Epimedium family, known to have anti-oxidative and anti-inflammatory activities. This study investigated the effects of Icariin on nuclear factor-kappa B (NF-ĸB) signaling pathway in intestinal epithelial cells (IEC) and macrophages, and in acute and chronic murine colitis models.

Methods

Human IEC line COLO 205 and murine macrophage cell line RAW 264.7 were pretreated with Icariin and then stimulated with tumor necrosis factor-α (TNF-α) and lipopolysaccharide respectively for in vitro studies. The expression of pro- and anti-inflammatory cytokines were evaluated by real-time RT-PCR (TNF- α, IL-6, IL-8, IL-12, and IL-10), and the effect of Icariin on NF-ĸB signaling pathway was examined by immunoblot analysis to detect IĸBα phosphorylation and degradation. Dextran sulfate sodium (DSS)-induced acute colitis in C57BL/6 wild-type mice and chronic colitis in IL-10-/- mice were treated with or without Icariin for in vivo studies. The severity of colitis was evaluated by daily body weight change, colon length, and colonic tissue histopathology.

Results

Icariin significantly attenuated the production of pro-inflammatory cytokines and degeneration of anti-inflammatory cytokines, and alleviated IĸBα phosphorylation and degradation in both IEC and murine macrophages stimulated by TNF-α and LPS, respectively. Icariin also significantly reduced the severity of colitis in both DSS-induced acute colitis model and chronic colitis in IL-10-/- mice models.

Conclusion

Icariin inhibits NF-ĸB signaling in both IECs and macrophages, and attenuates experimental murine colitis. These results suggest that Icariin may be a potential novel therapeutic agent for inflammatory bowel disease.