Effect of Xielitang on TLR4/NF-κB/HIF-1α Signaling Pathway in Mice with Ulcerative Colitis
10.13422/j.cnki.syfjx.20230239
- VernacularTitle:燮理汤对溃疡性结肠炎小鼠TLR4/NF-κB/HIF-1α通路的影响
- Author:
Xiaotian WANG
1
;
Yue WANG
2
;
Yaning BIAO
1
;
Jingmiao GAO
1
;
Li LI
3
;
Yangzi LU-AI
1
;
Yunjie YIN
1
;
Yixin ZHANG
1
Author Information
1. Hebei University of Chinese Medicine， International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine（TCM）of Hebei Province，Application Technology Research and Development Center of TCM in Hebei Universities，Shijiazhuang 050200，China
2. Department of Chinese Materia Medica，Cangzhou Hospital of integrated TCM-WM·Hebei， Cangzhou 061001，China
3. College of Pharmacy， Hebei Medical University，Shijiazhuang 050011，China
- Publication Type:Journal Article
- Keywords:
Xielitang;
ulcerative colitis;
dextran sodium sulfate;
Toll like receptor 4 （TLR4）;
nuclear transcription factor-κB （NF-κB）;
hypoxia inducible factor-1α （HIF-1α）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(8):142-149
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the protective effect of Xielitang on ulcerative colitis （UC） mice induced by dextran sodium sulfate （DSS） and its possible mechanism. MethodSixty C57BL/6 mice were randomly divided into normal group， model group， sulfasalazine group and and low-， medium-， and high-dose Xielitang groups. Free drinking DSS solution to build the chronic UC model mice. Except for normal group， other groups were given 1.5% DSS for 3 cycles of drinking （days 1-7， days 22-28 and days 43-49） and distilled water for the rest of the time （days 8-21， days 29-42 and days 50-63）. After the first cycle， corresponding drugs were given for 42 days. The changes of general condition， body weight and disease activity index （DAI） score of mice were daily recorded during the experiment. At the end of the treatment， serum and colon tissue samples were collected， colon length was measured， intestinal weight index and colonic mucosal injury （CMDI） score were calculated. The pathological status of colon tissue was observed by hematoxylin-eosin （HE） staining. The levels of interleukin-6 （IL-6）， interleukin-10 （IL-10） and tumour necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. The gene and protein expressions of Toll like receptor 4 （TLR4）， nuclear transcription factor-κB （NF-κB） and hypoxia inducible factor-1α （HIF-1α） in colon tissue was detected by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the normal group， the body weight， colon length and IL-10 content in the model group were significantly decreased （P<0.01）， DAI score， intestinal weight index， CMDI score， IL-6 and TNF-α contents， and mRNA and protein expression levels of TLR4， NF-κB and HIF-1α in the model group were significantly increased （P<0.01）. Moreover， the structure of colonic mucosa was destroyed and inflammatory cells infiltrated in the model group. Compared with model group， body weight， colon length and IL-10 content in each dose group of Xielitang were significantly increased （P<0.05， P<0.01）， DAI score， intestinal weight index and CMDI score， IL-6 and TNF-α contents， mRNA and protein expression levels of TLR4， NF-κB and HIF-1α were notably decreased （P<0.05， P<0.01）. The pathological injury of colon was obviously alleviated. ConclusionXielitang can significantly improve the inflammatory response of UC mice induced by DSS， and its mechanism may be related to the regulation of TLR4/NF-κB/HIF-1α signaling pathway.
