Protective effect of curcumin on TNBS-induced intestinal inflammation is mediated through the JAK/STAT pathway

Xingxing Zhang, Jian Wu, Bo Ye, Qiong Wang, Xiaodong Xie, Hong Shen

Curcumin displays a protective role in rat models of intestinal inflammation. However, the mechanism of how curcumin affects on intestinal inflammation is less known. The purpose of the current study is to explore the signal pathway in which the curcumin protecting rat from intestinal inflammation. The intestinal inflammation rat models were made by TNBS treatment. Curcumin was added to their diet 5 days before the TNBS instillation. After that, body weight change, score of macroscopic assessment of disease activity and microscopic scoring were utilized to analyse the severity of the induced inflammation. In addition, the level of pro-inflammatory cytokines and anti-inflammatory were detected to determine the effect of curcumin on intestinal inflammation. The JAK/STAT pathway of pro-inflammation response was also evaluated. Finally, the impact of curcumin on apoptosis in intestinal inflammation was assessed by TUNEL staining. Rats pretreated with curcumin significantly reversed the decrease of body weight and increase of colon weight derived from TNBS-induced colitis. Histological improvement was observed in response to curcumin. In addition, curcumin attenuated TNBS-induced secretion of pro-inflammatory cytokines and M1/M2 ratio, while stimulated the secretion of anti-inflammatory cytokines. The inhibition of pro-inflammation response was mediated by SOCS-1, which could efficiently suppress JAK/STAT pathways. Furthermore, curcumin efficiently suppressed the TNBS-induced apoptosis, and reduced the accumulation of cytochrome C in cytosol. The anti-inflammatory effect of curcumin is realized by enhancing SOCS-1 expression and inhibiting JAK/STAT pathways. Curcumin also plays an anti-apoptotic role in TNBS-induced intestinal inflammation. We propose that curcumin may have therapeutic implications for human intestinal inflammation.