scholarly journals Sishen Pill Maintained Colonic Mucosal Barrier Integrity to Treat Ulcerative Colitis via Rho/ROCK Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xiao-Yun Zhang ◽  
Hai-Mei Zhao ◽  
Yi Liu ◽  
Xiu-Yun Lu ◽  
Yan-Zhen Li ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Signaling Pathway ◽  
Connexin 43 ◽  
Clinical Symptoms ◽  
Rho Kinase ◽  
Gastrointestinal Diseases ◽  
Mucosal Barrier ◽  
Trinitrobenzene Sulfonic Acid ◽  
Injury Score ◽  
Intestinal Mucosal Barrier

Sishen Pill (SSP) is a classical prescription of traditional Chinese medicine and often used to treat gastrointestinal diseases, including ulcerative colitis (UC). However, its mechanism is still unclear. We aimed to determine the mechanism of SSP in the treatment of UC by investigating if it maintains the integrity of the intestinal mucosal barrier via the Rho A/Rho kinase (ROCK) signaling pathway. Administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) successfully induced chronic UC in rats, while the treatment effect of SSP was evaluated by body weight change, colonic length, colonic weight, colonic weight index, histological injury score, and pathological injury score after colitis rats were treated for 7 days. TNF-α and IL-1β levels were analyzed by ELISA, and the proteins of PI3K/Akt and RhoA/ROCK signaling pathway and junction proteins expression were measured by western blotting assay, and the distribution of Claudin 5 was shown by immunofluorescence. SSP significantly improved the clinical symptoms of colitis in rats and reduced the expression of p-RhoA, ROCK1, PI3K, and Akt in the colon mucosa, while it increased the expression of p-Rac and related proteins (Claudin-5, JAM1, VE-cadherin, and Connexin 43). In addition, SSP increased p-AMPKα and PTEN proteins expression, decreased Notch1 level, and hinted that activation of the PI3K/Akt signaling pathway was inhibited. In conclusion, SSP effectively treated chronic colitis induced by TNBS, which may have been achieved by inhibiting PI3K/Akt signal to suppress activation of the Rho/ROCK signaling pathway to finally maintain the integrity of the intestinal mucosal barrier.

scholarly journals Pingkui Enema Alleviates TNBS-Induced Ulcerative Colitis by Regulation of Inflammatory Factors, Gut Bifidobacterium, and Intestinal Mucosal Barrier in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hai-Feng Yun ◽  
Rui Liu ◽  
Dan Han ◽  
Xin Zhao ◽  
Jin-Wei Guo ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Survival Rate ◽  
Serum Concentration ◽  
Mucosal Barrier ◽  
Inflammatory Factors ◽  
High Dose ◽  
Trinitrobenzene Sulfonic Acid ◽  
Sprague Dawley ◽  
Intestinal Mucosal Barrier ◽  
Intestinal Mucus

Background. Ulcerative colitis (UC) is a chronic recurrent inflammation of the colon, and clinical outcome of UC is still unsatisfied. Pingkui enema, a traditional Chinese medicine prescription, has been safely applied for the treatment of diarrhea and dysentery in clinic for many years. However, its mechanism is still elusive. The present study is designed to investigate the effect of Pingkui enema on trinitrobenzene sulfonic acid- (TNBS-) induced ulcerative colitis (UC) and possible mechanism in rats. Methods. UC was induced by intracolonic instillation of TNBS in male Sprague-Dawley rats, which were treated with different dosages of Pingkui enema (low, medium, and high) or sulfasalazine for ten days. Survival rate was calculated. A clinical disease activity score was evaluated. Histological colitis severity was analyzed by hematoxylin-eosin (HE) staining. Content of Bifidobacterium in intestinal tissue was analyzed by RT-PCR. Concentration of IL-8, IL-13, TNF-α, D-lactic acid (D-LA), and diamine oxidase (DAO) in serum and contents of adhesin and receptor of Bifidobacterium adhesion in rat intestinal mucus were measured by ELISA. Results. The results showed that Pingkui enema treatment with high dosage markedly improved the survival rate compared with untreated and sulfasalazine treated groups. All dosages of Pingkui enema reduced pathological score. High dosage of Pingkui enema and sulfasalazine treatments significantly reduced the serum concentration of IL-8, TNF-α, D-LA, and DAO and markedly increased the serum concentration of IL-13. In addition, high-dose Pingkui enema and sulfasalazine treatments increased gut content of Bifidobacterium, gut mucus expressions of adhesin, and adhesin receptor of Bifidobacterium. Conclusions. Pingkui enema has therapeutic effect on TNBS-induced UC, and possible mechanism may be via regulation of gut probiotics (Bifidobacterium) and inflammatory factors and protection of intestinal mucosal barrier.

scholarly journals Mechanism underlying effect of Sijunzi decoction on intestinal mucosal barrier of mice with ulcerative colitis

2015 ◽  
Vol 23 (27) ◽  
pp. 4326
Author(s):  
Jing-Yu Huang ◽  
Hui Nong ◽  
Xian Pei ◽  
Xue Huang ◽  
Zhi-Rou Tan ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mucosal Barrier ◽  
Intestinal Mucosal Barrier

scholarly journals MiR-126 impairs the intestinal barrier function via inhibiting S1PR2 mediated activation of PI3K/AKT signaling pathway

2017 ◽  
Author(s):  
Tanzhou Chen ◽  
Haibo Xue ◽  
Ruoyang Lin ◽  
Zhiming Huang
Keyword(s):  
Signaling Pathway ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Akt Signaling ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Intestinal Mucosal Barrier ◽  
Pathological Tissues

AbstractBackgroundAberrant expression of miRNAs was a critical element in the pathogenesis of inflammatory bowel disease (IBD). This study aimed to explore the involvement and mechanism of miR-126 in IBD.MethodsIn this study, the endogenous expressions of miR-126, S1PR2 and S1P in the pathological tissues of patients with IBD were detected using qRT-PCR and western blot assay, respectively. The luciferase reporter gene assay was performed to confirm the targeting regulatory relation between miR-126 and S1PR2. The transendothelial electrical resistance assay was used to measured the value of TEER.ResultsThe expressions of miR-126, S1PR2 and S1P in the pathological tissues of IBD patients were significantly higher than that of the control group. Moreover, miR-126 overexpression contributed to intestinal mucosal barrier dysfunction in vitro. S1PR2 was a direct target of miR-126, and S1PR2 expression was negatively regulated by miR-126 in Caco-2 cells. However, S1PR2 activated by S1P had the protection effect for the integrity and permeability of intestinal mucosal barrier via a PI3K/Akt dependent mechanism. MiR-126 silencing possessed obvious protective effects on the intestinal barrier function, but these effects could be reversed by JTE-013 or LY294002.ConclusionMiR-126 down-regulated S1PR2 and then prevented the activation of PI3K/AKT signaling pathway, which ultimately could damage intestinal mucosal barrier function.

scholarly journals Protective effects of oxymatrine against DSS-induced acute intestinal inflammation in mice via blocking the RhoA/ROCK signaling pathway

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Yifan Wang ◽  
Zhexing Shou ◽  
Heng Fan ◽  
Meng Xu ◽  
Qianyun Chen ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Signaling Pathway ◽  
Intestinal Inflammation ◽  
Rho Kinase ◽  
Treg Cells ◽  
Positive Control ◽  
Protective Effects ◽  
Therapeutic Benefits ◽  
Wide Range ◽  
High Doses

Abstract Oxymatrine (OMT) is an important quinoxaline alkaloid that has a wide range of pharmacological effects and has been shown to alleviate ulcerative colitis due to its profound anti-inflammatory effects. The RhoA/ROCK (Rho kinase) signaling pathway has been shown to be related to the pathogenesis of several autoimmune diseases; however, the specific mechanisms of RhoA/ROCK signaling in inflammatory bowel disease (IBD) remain elusive. Therefore, we sought to determine whether OMT could ameliorate acute intestinal inflammation by targeting the RhoA/ROCK signaling pathway. The potential therapeutic effect of OMT on acute intestinal inflammation and its impact on the RhoA/ROCK signaling pathway were assessed in six groups of mice treated with low, medium and high doses of OMT (25, 50 and 100 mg/kg, respectively), and an inhibitor of ROCK, Y-27632, as a positive control, after initiating dextran sodium sulfate (DSS)-induced acute intestinal inflammation. The model group and normal group were injected intraperitoneally with equal doses of PBS. Our results showed that OMT treatment could protect the integrity of the epithelial barrier, relieve oxidative stress, inhibit the expression of inflammatory mediators and pro-inflammatory cytokines, restrain the differentiation of Th17 cells and promote the differentiation of Treg cells via inhibition of the RhoA/ROCK pathway, thus providing therapeutic benefits for ulcerative colitis (UC). Therefore, inhibiting the RhoA/ROCK pathway might be a new approach that can be used in UC therapy, which deserves to be investigated further.

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