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, 2019, 9306283
eCollection

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

Affiliations

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

Ma Fangxiao et al. Evid Based Complement Alternat Med.

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.

Conflict of interest statement

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
ROS generation in the mouse colon tissues and neutrophils of different groups. Bars of the two colors, respectively, indicate the ROS generation in the mouse colon tissues and neutrophils. Mice in the model control group, low TWP, middle TWP, and high TWP groups were provided a 5% DSS solution for one week. Meanwhile, the low TWP, middle TWP, and high TWP groups received different doses of TWP for 2 weeks. At the end of the experiment, the mouse colon tissues and neutrophils of each group were taken for the ROS content detection via the DCFH-DA (10 mM) fluorescence method. The results showed that the ROS in the colon tissues and neutrophils of the different TWP groups was significantly lower than that of the model control group and higher than that of the normal control group. ROS content decreases with the increased dose of TWP, and the differences among the TWP groups were significant. Each bar represents mean ± SD (n = 9); P < 0.05 vs. model; P < 0.05 vs. low TWP; P < 0.05 vs. middle TWP.
Figure 2
Figure 2
NOXs activity in the colon tissues and neutrophils of different groups. Bars of the two colors, respectively, indicate the NOXs activity in the mouse colon tissues and neutrophils. Mice in the model control, low TWP, middle TWP, and high TWP groups were provided a 5% DSS solution for one week. Meanwhile, the low TWP, middle TWP, and high TWP groups received different doses of TWP for 2 weeks. At the end of the experiment, the mouse colon tissues and neutrophils of each group were taken for the NOXs activity detection based on the NADPH consumption rate. The results showed that NOXs activity in the colon tissues and neutrophils of the different TWP groups was significantly lower than that of the model control group and higher than that of the normal control group. NOXs activity decreases with the increased dose of TWP, and the differences among the TWP groups were significant. Each bar represents mean ± SD (n = 9); P < 0.05 vs. model; P < 0.05 vs. low TWP; P < 0.05 vs. middle TWP.
Figure 3
Figure 3
The mRNA expression of NLRP3, ASC, and caspase-1 in neutrophils. Bars of the three colors, respectively, indicate the mRNA expression of NLRP3, ASC, and caspase-1 in neutrophils. Mice in the model control, low TWP, middle TWP, and high TWP groups were provided a 5% DSS solution for one week. Meanwhile, the low TWP, middle TWP, and high TWP groups received different doses of TWP for 2 weeks. At the end of the experiment, the mouse colon neutrophils of each group were taken for the detection of the mRNA expression of NLRP3, ASC, and caspase-1 via real-time PCR. The results showed that the mRNA expression of NLRP3, ASC, and caspase-1 in neutrophils of the different TWP groups was significantly lower than that of the model control group and higher than that of the normal control group. The mRNA expression of NLRP3, ASC, and caspase-1 decreases with the increased dose of TWP, and the differences among the TWP groups were significant. Each bar represents mean ± SD (n = 9); P < 0.05 vs. model; P < 0.05 vs. low TWP; P < 0.05 vs. middle TWP.
Figure 4
Figure 4
The mRNA expression of NLRP3, ASC, and caspase-1 in the colon tissues. Bars of the three colors, respectively, indicate the mRNA expression of NLRP3, ASC, and caspase-1 in the colon tissues. Mice in the model control, low TWP, middle TWP, and high TWP groups were provided a 5% DSS solution for one week. Meanwhile, the low TWP, middle TWP, and high TWP groups received different doses of TWP for 2 weeks. At the end of the experiment, the mouse colon tissues of each group were taken for the detection of the mRNA expression of NLRP3, ASC, and caspase-1 via real-time PCR. The results showed that the mRNA expression of NLRP3, ASC, and caspase-1 in the colon tissues of the different TWP groups was significantly lower than that of the model control group and higher than that of the normal control group. The mRNA expression of NLRP3, ASC, and caspase-1 decreases with the increased dose of TWP, and the differences among the TWP groups were significant. Each bar represents mean ± SD (n = 9); P < 0.05 vs. model; P < 0.05 vs. low TWP; P < 0.05 vs. middle TWP.

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References

    1. Xavier R. J., Podolsky D. K. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448(7152):427–434. doi: 10.1038/nature06005. - DOI - PubMed
    1. Xu W. B., Chen Y., Zhang T., et al. Functional role for NLRP-3 inflammasome and CCL-3 in DSS-induced ulcerative colitis. Chinese Journal of Integrated Traditional and Western Medicine. 2016;24(6):418–421.
    1. Su J., Liu Z. J. The expression of interleukin-25 in patients with inflammatory bowel disease and its clinical significance. Chinese Journal of Digestive Diseases. 2010;30(12):872–876.
    1. León A. J., Gómez E., Garrote J. A., et al. High levels of proinflammatory cytokines, but not markers of tissue injury, in Unaffected Intestinal Areas from Patients with IBD. Mediators of Inflammation. 2009;2009:10. doi: 10.1155/2009/580450.580450 - DOI - PMC - PubMed
    1. Sugimoto K., Ogawa A., Mizoguchi E., et al. IL-22 ameliorates intestial inflammation in mouse model of ulcerative colitis. Journal of Clinical Investigation. 2008;118(2):534–544. doi: 10.1172/jci33194. - DOI - PMC - PubMed

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