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 O(2)(-) 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 O(2)(-) associated with the favourable expression of T-helper 1
cytokines and iNOS. Consistent with these observations,
nuclear factor kappa B (
NF-kappa B) 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.