Tripterygium glycosides suppress colitis via NOXs-ROS-NLRP3 inflamma-tory signaling pathways / 中国病理生理杂志

ABSTRACT

AIM: To observe the effect of Tripterygium glycosides on NOXs-ROS-NLRP3 inflammatory signa-ling pathways in the colon tissue in dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) mice, and to investi-gate the underlying mechanisms.METHODS: BALB/c mice were used and the mouse model of UC was established by DSS induction.The mice were randomly divided into 5 groups (model group, low-, medium-and high-dose Tripterygium glycosides groups, and normal group).The colon tissues were collected 21 d after Tripterygium glycosides gavage.The mRNA expression of NLRP3, ASC and caspase-1 in the colon tissues was detected by real-time PCR.The caspase-1 ex-pression in the colorectal mucosa was observed by immunohistochemical method.ELISA was used to detect the protein le- vels of IL-1α, TNF-αand IL-13.The production of reactive oxygen species (ROS) was measured by chemiluminescence technique, and the consumption rate of NADPH, which was inhibited by DPI, was analyzed to determine the activity of NADPH oxidases (NOXs).The neutrophils were isolated, and the ROS production, NOXs activity, and the mRNA ex-pression of NLRP3, ASC and caspase-1 were also detected.RESULTS: The colon tissues were abnormal with different de-grees in Tripterygium glycosides groups, and histopathological scores were lower than that in model group.In Tripterygium glycosides groups, in addition to the mRNA expression levels of caspase-1 in the colon tissues between normal group and high-dose group, ROS production, NOXs activity and the mRNA expression levels of NLRP3, ASC and caspase-1 in the colon tissues and colon-isolated neutrophils were lower than those in model group (P <0.05), and higher than those in normal group (P <0.05).The results of pairwise comparison for the efficacy of Tripterygium glycosides administration showed that the above indexes were statistically significant except the mRNA expression levels of caspase-1 between middle-dose group and high-dose group.Tripterygium glycosides administration significantly decreased the expression levels of proinflammatory cytokines IL-1αand TNF-αin the homogenates of colon tissues in the model mice (P <0.05).No differ-ence of IL-13 expression among the groups was observed.CONCLUSION: Tripterygium glycosides inhibits NOXs-ROS-NLRP3 inflammatory signaling pathways to reduce the expression of IL-1α, TNF-αand other proinflammatory cytokines, and attenuates DSS-induced ulcerative colitis in mice, by which the neutrophils might be involved in the process.