Dataset Information

Effect of Tripterygium wilfordii Polycoride on the NOXs-ROS-NLRP3 Inflammasome Signaling Pathway in Mice with Ulcerative Colitis.

ABSTRACT: Objective:To explore the effect of Tripterygium wilfordii polycoride (TWP) on the NADPH oxidases (NOXs)-reactive oxygen species (ROS)-NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathway and the possibility of using TWP to treat ulcerative colitis (UC). Methods:BALB/c mice were randomly divided into five groups: model control, low TWP, middle TWP, high TWP, and normal control groups. A UC model was established with dextran sulfate sodium. The determination of ROS was carried out by using the fluorescent probe DCFH-DA, and NOXs activity was detected based on the NADPH consumption rate. The mRNA expression levels of NLRP3, ASC, and caspase-1 in the colon tissues and neutrophils were assessed via real-time PCR. Results:The colon tissues were abnormal with different degrees in TWP groups with disease activity index and histopathological scores lower than those in the model group. In TWP groups, ROS generation, NOXs activity, and the mRNA expression levels of NLRP3, ASC, and caspase-1 in the colon tissues and colon-isolated neutrophils were remarkably lower than those in the model control group (P < 0.05) and higher than those in the normal group (P < 0.05). The results of pairwise comparison for the efficacy of TWP administration showed that the above indexes were statistically significant with the lowest expression in the high TWP group (P < 0.05) and the highest expression in the low TWP group (P < 0.05). Conclusion:TWP demonstrated anti-inflammatory effects on UC by decreasing the expression of proinflammatory factors in the NOXs-ROS-NLRP3 signaling pathway.

SUBMITTER: Fangxiao M

PROVIDER: S-EPMC6721241 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Effect of <i>Tripterygium wilfordii</i> Polycoride on the NOXs-ROS-NLRP3 Inflammasome Signaling Pathway in Mice with Ulcerative Colitis.

Fangxiao Ma M Yifan Ke K Jihong Zhong Z Yan Shen S Yingchao Liu L

Evidence-based complementary and alternative medicine : eCAM 20190821

<h4>Objective</h4>To explore the effect of <i>Tripterygium wilfordii</i> polycoride (TWP) on the NADPH oxidases (NOXs)-reactive oxygen species (ROS)-NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathway and the possibility of using TWP to treat ulcerative colitis (UC).<h4>Methods</h4>BALB/c mice were randomly divided into five groups: model control, low TWP, middle TWP, high TWP, and normal control groups. A UC model was established with dextran sulfate sodium. The determination of ...[more]

PMID: 31531121

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Project description:BackgroundAccording to the Chinese Pharmacopoeia, the fruit of Schisandra chinensis (Turcz.) Baill. (SC) is an important traditional Chinese medicine that can be used to treat diarrhea. Despite the increasing research on the anti-inflammatory and anti-oxidant aspects of SC, the studies on the anti-ulcerative colitis of Schisandrin (SCH), the main constituent of SC, are relatively few.MethodsThe mice used in the study were randomly distributed into 6 groups: control, model, 5-ASA, and SCH (20, 40, 80 mg/kg/d). The mice in the model group were administered 3% (w/v) dextran sulfate sodium (DSS) through drinking water for 7 days, and the various parameters of disease activity index (DAI) such as body weight loss, stool consistency, and gross blood were measured. ELISA was used to detect inflammatory factors, and bioinformatics combined with transcriptome analysis was done to screen and verify relevant targets. 16S rDNA high-throughput sequencing was used to analyze the composition of the gut microbiota(GM), while mass spectrometry was done to analyze the changes in the content of bile acids (BAs) in the intestine.ResultsMice treated with SCH experienced significant weight gain, effectively alleviating the severity of colitis, and decreasing the levels of inflammatory factors such as TNF-α, IL-1β, IL-18, IL-6, and other related proteins (NLRP3, Caspase-1, SGK1) in UC mice. Furthermore, the analysis of GM and BAs in mice revealed that SCH increased the relative abundance of Lactobacilli spp, reduced the relative abundance of Bacteroides, and promoted the conversion of primary BAs to secondary BAs. These effects contributed to a significant improvement in the DSS-induced GM imbalance and the maintenance of intestinal homeostasis.ConclusionIt seems that there is a close relationship between the SCH mechanism and the regulation of SGK1/NLRP3 pathway and the restoration of GM balance. Therefore, it can be concluded that SCH could be a potential drug for the treatment of UC.

Dataset Information

Effect of Tripterygium wilfordii Polycoride on the NOXs-ROS-NLRP3 Inflammasome Signaling Pathway in Mice with Ulcerative Colitis.

Publications

Effect of <i>Tripterygium wilfordii</i> Polycoride on the NOXs-ROS-NLRP3 Inflammasome Signaling Pathway in Mice with Ulcerative Colitis.

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