Isoflavone formononetin（FN） is a main active component of red clover（Trifolium pratense L.）, a medicinal plant possessing antitumorigenic and antioxidant properties. In the present study, we aimed to examine the effect of FN on dextran sulfate sodium（DSS）-induced ulcerative colitis（UC） in mice. The results showed that FN（25, 50 mg/kg） markedly attenuated the loss of body weight, the disease activity index（DAI）, shortening of colon length and tissue injury induced by DSS treatment. In addition, the levels of tumor necrosis factor-α（TNF-α）, interleukin-6（IL-6）, and cyclooxygenase-2（COX-2） were also significantly reduced in FN treatment group compared with the DSS group. Moreover, several representative oxidative stress parameters in colorectum, including superoxide dismutase（SOD）, methane dicarboxylic aldehyde（MDA）, myeloperoxidase（MPO） and 8-oxoguanine, were markedly ameliorated. In this study, we also found that the expression of Nrf2 was increased by FN treatment. However, symptoms of UC were not ameliorated in Nrf2 knockout mice. Taken together, FN could prevent the development of UC through activating of Nrf2 axis, and the protective effect was Nrf2 dependent. Our results demonstrated that FN might be a potential therapeutic agent in the treatment of UC.
