Green tea EGCG effectively alleviates experimental colitis in middle-aged male mice by attenuating multiple aspects of oxi-inflammatory stress and cell cycle deregulation.

Abstract

Age-dependent increased risk of inflammatory bowel diseases such as ulcerative colitis is being increasingly realized, and yet therapies targeting this disorder within the purview of aging are limited. The present study attempted to assess the efficacy of green tea epigallocatechin gallate (EGCG) consumption in preventing the severity and progression of dextran sulphate sodium (DSS)-induced ulcerative colitis in 18months old middle-aged male mice. Acute colitis was induced in animals using DSS and protective effects of EGCG consumption were examined. Different parameters related to disease progression and molecular markers related to oxi-inflammatory stress, localized and systemic cytokine response, epithelial barrier integrity, and cell cycle progression profile were evaluated. DSS treatment induced rapid and severe symptoms of colitis such as consistently increased DAI score, shortened and inflamed colon accompanied by increased levels of inflammatory proteins (TNFα/IL-6/IL-1β) in both the colon tissue and cultured splenocytes indicating exaggerated Th1 immune response. Markers of oxidative stress increased while antioxidant defences and the expression of tight junction genes in the colonic cells were attenuated. Dysregulation in the expression of cell cycle inhibitory genes (p53/p21WAF1/p16Ink4a) indicated possible induction of colitis-induced dysplasia. On the other hand, EGCG consumption strongly attenuated all the measured ostensible as well as molecular markers of the disease progression as evidenced by improved DAI score, cellular antioxidant capacity, attenuated Th1 cytokine response both in the colon and cultured splenocytes, enhanced expression of tight junction genes, and cell cycle inhibitors thereby suggesting systemic effects of EGCG. Together, these observations suggest that drinking EGCG-rich green tea can be a significant way of managing the severity of colitis during aging.