Epigallocatechin-3-gallate (EGCG) ameliorates dextran sulfate sodium (DSS) –induced inflammatory bowel disease

Abstract

Abstract Background Given the potential side effects associated with conventional medical treatment of Inflammatory Bowel Disease (IBD), dietary supplements have been investigated by several groups. We tested if epigallocatechin gallate (EGCG) may be beneficial in IBD. Methods 36 C57BL/6J mice were subjected to dextran sulfate sodium (DSS)-induced IBD and divided into 3 groups: model group (MD; no EGCG), low dose EGCG group (LE, 20 mg/kg/d) and high dose EGCG group (HE, 50 mg /kg/d). Results Both high and low dose EGCG treatment alleviated clinical manifestations of IBD including body weight loss and disease activity index (DAI): HE: 3.3 and LE: 2.8 vs. 8.3 in MD (p < 0.001, n=8–10 mice/group). Macroscopic severity score (MSS) of HE and LE groups were 2.4, and 2.2, respectively, significantly lower than in MD (5.0, P < 0.01). The mean colon length of MD group was 5.8 cm; treatment with EGCG restored colon length (HE: 6.5 cm; LE: 6.4 cm). Intestinal permeability was improved as demonstrated by FITC-Dextran assay (HE: 3.28; LE: 2.85, vs. MD group: 6.69 ng/ml, P < 0.001) .The colitis histology score of HE (1.54) and LE (0.42) groups were significantly lower than that in MD (4.3, P < 0.001). In addition, EGCG treatment reduced colonic levels of pro-inflammatory cytokines: IL-6 (HE: 0.45; LE group: 0.41 vs MD: 0.89 ng/g tissue, P =0.03), MCP-1 (HE: 1.83; LE: 1.87, vs MD: 3.5 ng/g tissue P = 0.01) and TNF-alpha (HE: 8.87; LE: 10 vs MD: 21.7 ng/g tissue, P <0.001). Lower CD3+ T cell and CD68+ macrophage infiltration was also noted in HE and LE mice (P < 0.001), compared to MD controls. Conclusion These results underscore the therapeutic potential of EGCG in the treatment of IBD, which appear to be mediated through multiple inflammatory pathways.