Thearubigin, the major polyphenol of black tea, ameliorates mucosal injury in trinitrobenzene sulfonic acid-induced colitis

Abstract

Inflammatory bowel disease is characterized by oxidative and nitrosative stress, leukocyte infiltration and upregulation of proinflammatory cytokines. The aim of the present study was to examine the protective effects of thearubigin, an anti-inflammatory and anti-oxidant beverage derivative, on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice, a model for inflammatory bowel disease. Intestinal lesions (judged by macroscopic and histological score) were associated with neutrophil infiltration (measured as increase in myeloperoxidase activity in the mucosa), increased serine protease activity (may be involved in the degradation of colonic tissue) and high levels of malondialdehyde (an indicator of lipid peroxidation). Both nitric oxide (NO) and O₂^- were increased with concomitant upregulation in the mRNA expression of proinflammatory cytokine response and inducible NO synthase (iNOS). Dose-response studies revealed that pretreatment of mice with thearubigin (40 mg kg^-1 day^-1, i.g. for 10 days) significantly ameliorated the appearance of diarrhoea and the disruption of colonic architecture. Higher dose (100 mg kg^-1) had comparable effects. This was associated with a significant reduction in the degree of both neutrophil infiltration and lipid peroxidation in the inflamed colon as well as decreased serine protease activity. Thearubigin also reduced the levels of NO and O₂^- associated with the favourable expression of T-helper 1 cytokines and iNOS. Consistent with these observations, nuclear factor kappa B (NF-κB) activation in colonic mucosa was suppressed in thearubigin-treated mice. The results of this study suggest that thearubigin, the most predominant polyphenol of black tea, exerts beneficial effects in experimental colitis and may, therefore, be useful in the treatment of inflammatory bowel disease.