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[Effect of Tripterygium wilfordii polycoride upon inflammation and TLR4/MyD88 signaling pathway in ulcerative colitis rats model].
Zhonghua Yi Xue Za Zhi. 2016 May 17; 96(18):1444-9.ZY

Abstract

OBJECTIVE

To observe the effect of Tripterygium wilfordii polycoride (TWP) on ulcerative colitis (UC), and its intervention effect on toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, thus to investigate its possible mechanism.

METHODS

Trinitrobenzene sulfonic acid (TNBS)/ethanol enema method was used to set up the UC rat model. With random number table, 90 male Wistar rats were divided into normal control group, model group, TWP low, medium and high dose group (3, 6, 12 mg/kg, respectively) and azathioprine (AZA) group (6 mg/kg), with 15 rates in each group. Four days after enema, rates in each group were given corresponding drug lavage for 14 consecutive days. Disease activity index (DAI), colon gross morphological damage and histological grading of each group were observed. Using Western blot and reverse transcription (RT)-PCR method, the TLR4/MyD88 signaling pathway-related proteins in UC rat intestinal tissue were detected, namely TLR4, MyD88, tumor necrosis factor receptor related factor 6 (TRAF-6), nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β).

RESULTS

The DAI, colon gross morphological damage, and histological grading of the model group were significantly higher than that of the normal control group (all P<0.01), indicating successful establishment of UC model. The DAI, colon gross morphological damage and histological grading of the TWP high dose group were lower than those of the model group (0.87±0.25 vs 1.60±0.76, 3.93±1.94 vs 5.40±2.21, 5.45±2.73 vs 13.27±3.50, P<0.05). Compared with the normal control group, the mRNA and protein expressions of TLR4, MyD88, TRAF-6, NF-κB, TNF-α, and IL-1β in the model group rats were significantly increased (all P<0.01); which were significantly decreased in the TWP high dose group compared with model group rats (mRNA: 2.166±0.475 vs 5.647±0.275, 1.295±0.087 vs 3.774±0.418, 1.125±0.188 vs 2.535±0.320, 1.201±0.152 vs 2.082±0.077, 1.525±0.218 vs 3.094±0.022, 1.797±0.257 vs 17.152±0.145; protein: 0.252±0.010 vs 0.277±0.008, 0.172±0.002 vs 0.213±0.005, 0.233±0.006 vs 0.248±0.003, 0.099±0.003 vs 0.122±0.007, 0.238±0.002 vs 0.252±0.005, 0.235±0.003 vs 0.245±0.006, all P<0.05), also decreased in the AZA group (all P<0.01); and there were no significant differences between the TWP high dose group and the AZA group (all P>0.05).

CONCLUSIONS

TWP can alleviate intestinal inflammation, promote healing of mucosa, showing a therapeutic effect for UC. One of its mechanisms may be through inhibiting the expression of TLR4, affecting the expression of TRAF-6, which is downstream to MyD66 signaling pathway, thus to suppress the activation of NF-κB and reduce the release of inflammatory factor such as TNF-α and IL-1β.

Authors+Show Affiliations

First Clinical Medical College of Zhejiang Chinese Medical University, Department of Gastroenterology of First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

27266354

Citation

Qin, D P., et al. "[Effect of Tripterygium Wilfordii Polycoride Upon Inflammation and TLR4/MyD88 Signaling Pathway in Ulcerative Colitis Rats Model]." Zhonghua Yi Xue Za Zhi, vol. 96, no. 18, 2016, pp. 1444-9.
Qin DP, Sun PN, Zhou YJ, et al. [Effect of Tripterygium wilfordii polycoride upon inflammation and TLR4/MyD88 signaling pathway in ulcerative colitis rats model]. Zhonghua Yi Xue Za Zhi. 2016;96(18):1444-9.
Qin, D. P., Sun, P. N., Zhou, Y. J., Chen, F. M., Zhang, C. L., Han, J. X., & Yang, X. J. (2016). [Effect of Tripterygium wilfordii polycoride upon inflammation and TLR4/MyD88 signaling pathway in ulcerative colitis rats model]. Zhonghua Yi Xue Za Zhi, 96(18), 1444-9. https://doi.org/10.3760/cma.j.issn.0376-2491.2016.18.012
Qin DP, et al. [Effect of Tripterygium Wilfordii Polycoride Upon Inflammation and TLR4/MyD88 Signaling Pathway in Ulcerative Colitis Rats Model]. Zhonghua Yi Xue Za Zhi. 2016 May 17;96(18):1444-9. PubMed PMID: 27266354.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Effect of Tripterygium wilfordii polycoride upon inflammation and TLR4/MyD88 signaling pathway in ulcerative colitis rats model]. AU - Qin,D P, AU - Sun,P N, AU - Zhou,Y J, AU - Chen,F M, AU - Zhang,C L, AU - Han,J X, AU - Yang,X J, PY - 2016/6/9/entrez PY - 2016/6/9/pubmed PY - 2016/10/7/medline SP - 1444 EP - 9 JF - Zhonghua yi xue za zhi JO - Zhonghua Yi Xue Za Zhi VL - 96 IS - 18 N2 - OBJECTIVE: To observe the effect of Tripterygium wilfordii polycoride (TWP) on ulcerative colitis (UC), and its intervention effect on toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, thus to investigate its possible mechanism. METHODS: Trinitrobenzene sulfonic acid (TNBS)/ethanol enema method was used to set up the UC rat model. With random number table, 90 male Wistar rats were divided into normal control group, model group, TWP low, medium and high dose group (3, 6, 12 mg/kg, respectively) and azathioprine (AZA) group (6 mg/kg), with 15 rates in each group. Four days after enema, rates in each group were given corresponding drug lavage for 14 consecutive days. Disease activity index (DAI), colon gross morphological damage and histological grading of each group were observed. Using Western blot and reverse transcription (RT)-PCR method, the TLR4/MyD88 signaling pathway-related proteins in UC rat intestinal tissue were detected, namely TLR4, MyD88, tumor necrosis factor receptor related factor 6 (TRAF-6), nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β). RESULTS: The DAI, colon gross morphological damage, and histological grading of the model group were significantly higher than that of the normal control group (all P<0.01), indicating successful establishment of UC model. The DAI, colon gross morphological damage and histological grading of the TWP high dose group were lower than those of the model group (0.87±0.25 vs 1.60±0.76, 3.93±1.94 vs 5.40±2.21, 5.45±2.73 vs 13.27±3.50, P<0.05). Compared with the normal control group, the mRNA and protein expressions of TLR4, MyD88, TRAF-6, NF-κB, TNF-α, and IL-1β in the model group rats were significantly increased (all P<0.01); which were significantly decreased in the TWP high dose group compared with model group rats (mRNA: 2.166±0.475 vs 5.647±0.275, 1.295±0.087 vs 3.774±0.418, 1.125±0.188 vs 2.535±0.320, 1.201±0.152 vs 2.082±0.077, 1.525±0.218 vs 3.094±0.022, 1.797±0.257 vs 17.152±0.145; protein: 0.252±0.010 vs 0.277±0.008, 0.172±0.002 vs 0.213±0.005, 0.233±0.006 vs 0.248±0.003, 0.099±0.003 vs 0.122±0.007, 0.238±0.002 vs 0.252±0.005, 0.235±0.003 vs 0.245±0.006, all P<0.05), also decreased in the AZA group (all P<0.01); and there were no significant differences between the TWP high dose group and the AZA group (all P>0.05). CONCLUSIONS: TWP can alleviate intestinal inflammation, promote healing of mucosa, showing a therapeutic effect for UC. One of its mechanisms may be through inhibiting the expression of TLR4, affecting the expression of TRAF-6, which is downstream to MyD66 signaling pathway, thus to suppress the activation of NF-κB and reduce the release of inflammatory factor such as TNF-α and IL-1β. SN - 0376-2491 UR - https://www.unboundmedicine.com/medline/citation/27266354/[Effect_of_Tripterygium_wilfordii_polycoride_upon_inflammation_and_TLR4/MyD88_signaling_pathway_in_ulcerative_colitis_rats_model]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&amp;issn=0376-2491&amp;year=2016&amp;vol=96&amp;issue=18&amp;fpage=1444 DB - PRIME DP - Unbound Medicine ER -