The preventive effect and underlying mechanism of Mill. fruits on dextran sulphate sodium-induced ulcerative colitis in mice.

The purpose of this research was to explore the preventive effect of an 80% ethanol extract of Mill. fruits on dextran sulfate sodium (DSS)-induced colitis in mice and to elucidate the underlying molecular mechanisms of this effect. The results indicated that the extract, especially when administered at a high dose, could dramatically decrease the disease activity index, maintain normal spleen conditions, and improve colonic histopathology and length in the DSS-induced mice. In addition, extract administration could significantly suppress the levels of malondialdehyde, myeloperoxidase, tumor necrosis factor-α, interleukin-1β, and interleukin-6 and enhance superoxide dismutase and glutathione levels. The extract obviously protected intestinal barrier integrity by improving Occludin, ZO-1 and Claudin-1 expression levels. Western blot and immunohistochemistry analyses further indicated that the preventive effect of the phenol-rich extract on DSS-induced colitis might be achieved through the up-regulation of the expression of several pivotal oxidative stress-associated proteins, namely Nrf2, NQO1 and HO-1, and the down-regulation of the expression of several pivotal inflammation-associated proteins, namely -NF-κB, -IκB, COX-2, iNOS, -P38, -Erk1/2, and -JNK. Therefore, fruits extract possesses the capability to prevent DSS-induced ulcerative colitis in mice and could be utilized as a natural substance in the exploitation of functional foods as an adjuvant dietary therapy for preventing and/or alleviating inflammatory bowel disease.